CLASSES

BOXED WARNING

Systemic quinolones have been associated with disabling and potentially irreversible serious adverse reactions such as tendinopathy, including tendinitis and tendon rupture requiring surgical repair or resulting in prolonged disability. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Because of this risk for serious and potentially permanent side effects, quinolones should only be used for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis in cases where alternative treatment options cannot be used. Discontinue quinolones at the first sign of tendon inflammation or tendon pain as these are symptoms that may precede rupture of the tendon. Avoid quinolone use in patients with a history of tendon disorders or tendon rupture. Tendon rupture typically involves the Achilles tendon; however, ruptures of the hand, shoulder, biceps, thumb, and other tendons have also been reported. Tendinitis and tendon rupture can occur bilaterally. Rupture can occur during therapy or up to a few months after therapy has been stopped. The risk of tendon rupture is further increased in older adults (more than 60 years of age), those receiving concomitant corticosteroid therapy, and in organ transplant recipients (including kidney, heart, and lung transplants). Reasons for tendon ruptures also include physical activity or exercise, kidney failure, or tendon problems in the past. If patients experience tendon inflammation or pain, they should rest and refrain from exercise until the diagnosis of tendonitis or tendon rupture has been confidently excluded.

Systemic quinolones have been associated with disabling and potentially irreversible serious neurotoxicity, including central nervous system effects and peripheral neuropathy. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Because of this risk for serious and potentially permanent side effects, quinolones should only be used for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis in cases where alternative treatment options cannot be used. Avoid quinolone use in patients who have previously experienced peripheral neuropathy. Additionally, use quinolones with caution in patients with a known or suspected CNS disorder (e.g., seizure disorder, severe cerebrovascular disease) or in the presence of other risk factors (e.g., certain drug therapy, renal dysfunction) that may predispose to seizures or lower seizure threshold. Therapy should be discontinued at the first signs or symptoms of neuropathy (e.g., pain, burning, tingling, numbness, weakness, or other alterations of sensation such as light touch, temperature, position sense, and vibratory sensation) or central nervous system adverse events (i.e., anxiety, confusion, convulsions, depression, hallucinations, severe headaches, increased intracranial pressure (including pseudotumor cerebri), insomnia, lightheadedness, nightmares, paranoia, restlessness, suicidal thoughts or acts, toxic psychosis, or tremors).

Myasthenia gravis

Avoid systemic quinolones, like ciprofloxacin, in patients with a history of myasthenia gravis. Quinolones may exacerbate the signs of myasthenia gravis and lead to life threatening weakness of the respiratory muscles. Serious postmarketing events, including deaths and the requirement for ventilatory support, have been associated with quinolone use in patients with myasthenia gravis. Because of this risk for serious and potentially permanent side effects, quinolones should only be used for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis in cases where alternative treatment options cannot be used.

DOSAGE & INDICATIONS

For the treatment of urinary tract infection (UTI), including acute uncomplicated cystitis and pyelonephritis.

For the treatment of acute, uncomplicated UTI (acute cystitis).

Oral dosage (regular tablets)

Adult females

250 mg PO every 12 hours for 3 days. Due to the risk for serious and potentially permanent side effects associated with fluoroquinolone antibiotics, ciprofloxacin should only be used in cases where alternative treatment options cannot be used.

Oral dosage (extended-release tablets)

Adult females

500 mg PO once daily for 3 days. Due to the risk for serious and potentially permanent side effects associated with fluoroquinolone antibiotics, ciprofloxacin should only be used in cases where alternative treatment options cannot be used.

For the treatment of mild to moderate UTIs and for the treatment of severe and/or complicated UTIs, including pyelonephritis.

Oral dosage (immediate-release formulations)

Adults

250 to 500 mg PO every 12 hours for 7 to 14 days. Clinical practice guidelines suggest a 7-day regimen with or without an initial intravenous dose is appropriate for patients with acute pyelonephritis not requiring hospitalization. For catheter-associated UTIs, clinical practice guidelines suggest that 7 days is appropriate for patients who have prompt resolution of symptoms and 10 to 14 days is recommended for those with a delayed response.

Children and Adolescents

10 to 20 mg/kg/dose PO every 12 hours (Max: 750 mg/dose) for 10 to 21 days (mean duration of treatment in studies was 11 days). Ciprofloxacin is not considered a drug of first choice due to increased incidence of adverse reactions. For pediatric patients aged 2 to 24 months, the American Academy of Pediatrics (AAP) does not include ciprofloxacin as an empiric treatment option. In general, the AAP suggests a treatment duration of 7 to 14 days.

Oral dosage (extended-release tablets)

Adults

1,000 mg PO once daily for 7 to 14 days.

Intravenous dosage

Adults

200 to 400 mg IV every 12 hours for 7 to 14 days. Clinical practice guidelines suggest an initial IV dose then a 7-day oral regimen is appropriate for patients with acute pyelonephritis not requiring hospitalization. For catheter-associated UTIs, clinical practice guidelines suggest that 7 days is appropriate for patients who have prompt resolution of symptoms and 10 to 14 days is recommended for those with a delayed response.

Children and Adolescents

6 to 10 mg/kg/dose IV every 8 hours (Max: 400 mg/dose) for 10 to 21 days (mean duration of treatment in studies was 11 days); may switch to oral therapy as appropriate. Ciprofloxacin is not considered a drug of first choice due to increased incidence of adverse reactions. For pediatric patients aged 2 to 24 months, the American Academy of Pediatrics (AAP) does not include ciprofloxacin as an empiric treatment option. In general, the AAP suggests a treatment duration of 7 to 14 days.

For the treatment of lower respiratory tract infections, including bronchitis, community-acquired pneumonia (CAP), and nosocomial pneumonia. NOTE: Ciprofloxacin is not a drug of first choice in the treatment of presumed or confirmed pneumonia secondary to Streptococcus pneumoniae.

For the treatment of nosocomial, ventialator-associated pneumonia (VAP) or hospital-acquired pneumonia (HAP).

Intravenous dosage

Adults

400 mg IV every 8 hours for 10 to 14 days. Clinical practice guidelines recommend treatment for 7 days. For patients with risk factors for gram-negative resistance or with a high mortality risk, add an antipseudomonal beta-lactam. In patients with risk factors for MRSA, add vancomycin or linezolid.

Oral dosage

Adults

500 to 750 mg PO every 12 hours for 7 to 14 days. Clinical practice guidelines recommend treatment for 7 days. Oral therapy is not addressed, but deescalation in general is recommended.

For the treatment of community-acquired pneumonia (CAP).

Intravenous dosage

Adults

400 mg IV every 8 to 12 hours for 7 to 14 days. Clinical practice guidelines recommend ciprofloxacin as a treatment option in combination with an antipneumococcal/antipseudomonal beta-lactam with or without an aminoglycoside in patients with CAP due to Pseudomonas. If MRSA is also suspected, linezolid or vancomycin should also be included. Clinical practice guidelines recommend treatment for a minimum of 5 days and the patient should be afebrile for 48 to 72 hours with no more than 1 sign of clinical instability before discontinuation.

Adolescents†

15 mg/kg/dose IV every 12 hours (Max: 400 mg/dose) is recommended by the Infectious Diseases Society of America (IDSA) as an alternative therapy for patients with severe beta-lactam allergy in infections due to Haemophilus influenzae. A treatment duration of 10 days is best studied, although shorter durations may be effective for some cases. For HIV-infected patients at risk for pneumonia due to Pseudomonas aeruginosa, HIV guidelines recommend 400 mg IV every 8 to 12 hours in combination with an antipneumococcal, antipseudomonal beta-lactam.

Infants 3 to 11 months† and Children†

15 mg/kg/dose IV every 12 hours (Max: 400 mg/dose) is recommended by the Infectious Diseases Society of America (IDSA) as an alternative therapy for patients with severe beta-lactam allergy in infections due to Haemophilus influenzae. A treatment duration of 10 days is best studied, although shorter durations may be effective for some cases.

Oral dosage

Adults

500 to 750 mg PO every 12 hours for 7 to 14 days. Clinical practice guidelines recommend ciprofloxacin as a treatment option in combination with an antipneumococcal/antipseudomonal beta-lactam with or without an aminoglycoside. If MRSA is also suspected, linezolid or vancomycin should also be included. Clinical practice guidelines recommend treatment for a minimum of 5 days and the patient should be afebrile for 48 to 72 hours with no more than 1 sign of clinical instability before discontinuation.

For the treatment of acute exacerbations of chronic bronchitis.

Intravenous dosage

Adults

400 mg IV every 8 to 12 hours for 7 to 14 days. Due to the risk for serious and potentially permanent side effects associated with fluoroquinolone antibiotics, ciprofloxacin should only be used in cases where alternative treatment options cannot be used.

Oral dosage

Adults

500 to 750 mg PO every 12 hours for 7 to 14 days. Due to the risk for serious and potentially permanent side effects associated with fluoroquinolone antibiotics, ciprofloxacin should only be used in cases where alternative treatment options cannot be used.

For the treatment of skin and skin structure infections, including diabetic foot ulcer, surgical incision site infections, animal bite wounds, and necrotizing infections.

For the treatment of diabetic foot ulcer.

Oral dosage

Adults

500 to 750 mg PO every 12 hours for 7 to 14 days. Clinical practice guidelines suggest ciprofloxacin in combination with clindamycin as an option for moderate to severe diabetic wound infections. Most patients with just skin and soft tissue infections do well with 1 to 2 weeks of therapy.

Intravenous dosage

Adults

400 mg IV every 8 to 12 hours for 7 to 14 days. Clinical practice guidelines suggest ciprofloxacin in combination with clindamycin as an option for moderate to severe diabetic wound infections. Most patients with just skin and soft tissue infections do well with 1 to 2 weeks of therapy.

For the treatment of surgical incision site infections.

Oral dosage

Adults

750 mg PO every 12 hours for 7 to 14 days. Clinical practice guidelines include ciprofloxacin in combination with metronidazole for incisional surgical site infections of the intestinal or genitourinary tracts or axilla or perineum.

Intravenous dosage

Adults

400 mg IV every 12 hours for 7 to 14 days. Clinical practice guidelines include ciprofloxacin in combination with metronidazole for incisional surgical site infections of the intestinal or genitourinary tracts or axilla or perineum.

For the treatment of animal bite wounds.

Oral dosage

Adults

500 to 750 mg PO every 12 hours for 7 to 14 days. In setting of a cat or dog bite, clinical practice guidelines also recommend pre-emptive antimicrobial therapy for 3 to 5 days for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

Intravenous dosage

Adults

400 mg IV every 12 hours for 7 to 14 days with an anaerobic agent (clindamycin or metronidazole). In setting of a cat or dog bite, clinical practice guidelines also recommend pre-emptive antimicrobial therapy for 3 to 5 days for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

For the treatment of necrotizing infections of the skin, fascia, and muscle.

Intravenous dosage

Adults

400 mg IV every 12 hours plus doxycycline for Aeromonas hydrophila infections. Surgical intervention is the primary therapeutic intervention. Antibiotic therapy should be administered until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours.

Oral dosage

Adults

500 to 750 mg PO every 12 hours for 7 to 14 days.

Intravenous dosage

Adults

400 mg IV every 8 to 12 hours for 7 to 14 days.

For the treatment of enteric infections, including acute gastroenteritis and infectious diarrhea.

For the treatment of uncomplicated gonorrhea (e.g., cervicitis and urethritis).

Oral dosage

Adults

Due to resistance, the CDC no longer recommends quinolones for treating gonococcal infections. FDA-approved labeling suggests 250 mg PO as a single dose. Use of high doses of systemic antibiotics for short periods of time to treat gonorrhea may mask or delay the symptoms of incubating syphilis. Serologic test for syphilis should be done at the time of diagnosis of gonorrhea. Patients treated with ciprofloxacin should have a follow-up serologic test for syphilis after 3 months as ciprofloxacin does not treat syphilis.

For the treatment of mild to moderate acute sinusitis.

Oral dosage

Adults

500 mg PO every 12 hours for 10 days. Ciprofloxacin is not included in clinical practice guidelines for sinusitis; other respiratory quinolones (levofloxacin, moxifloxacin) are preferred. Due to the risk for serious and potentially permanent side effects associated with fluoroquinolone antibiotics, they should only be used in cases where alternative treatment options cannot be used.

Intravenous dosage

Adults

400 mg IV every 12 hours. Ciprofloxacin is not included in clinical practice guidelines for sinusitis; other respiratory quinolones (levofloxacin, moxifloxacin) are preferred. Due to the risk for serious and potentially permanent side effects associated with fluoroquinolone antibiotics, they should only be used in cases where alternative treatment options cannot be used.

For empiric treatment of patients with febrile neutropenia as part of combination therapy.

For febrile neutropenia in adults.

Intravenous dosage

Adults

400 mg IV every 8 to 12 hours in combination with an antipseudomonal beta-lactam. Clinical practice guidelines suggest ciprofloxacin may be used as an adjunctive therapy in high-risk neutropenic patients.

10 to 12.5 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) has been studied in low-risk outpatients and is often administered after initial IV therapy. Treatment is generally continued until fever is absent for 24 to 48 hours with a rising neutrophil count. Oral therapy for low-risk outpatients with quinolones is suggested by the American Society of Clinical Oncology; however, quinolones are not part of the empiric treatment regimens for inpatients.

For the treatment of bacterial conjunctivitis.

Ophthalmic dosage (solution)

Adults

1 to 2 drops in affected eye(s) every 2 hours, while awake, for 2 days and then every 4 hours, while awake, for the next 5 days.

Infants, Children, and Adolescents

1 to 2 drops in affected eye(s) every 2 hours, while awake, for 2 days and then every 4 hours, while awake, for the next 5 days.

Neonates

1 to 2 drops in affected eye(s) every 2 hours, while awake, for 2 days and then every 4 hours, while awake, for the next 5 days.

Ophthalmic dosage (ointment)

Adults

1/2 inch ribbon to conjunctival sac 3 times per day for first 2 days, then 1/2 inch twice daily for the next 5 days.

Children and Adolescents 2 to 17 years

1/2 inch ribbon to conjunctival sac 3 times per day for first 2 days, then 1/2 inch twice daily for the next 5 days.

For the treatment of ophthalmic infection associated with corneal ulcer.

Ophthalmic dosage (solution)

Adults

2 drops in affected eye(s) every 15 minutes for 6 hours then every 30 minutes for the remainder of the first day. For the second day, 2 drops every 1 hour. For days 3 to 14, 2 drops every 4 hours. Treatment may be continued after 14 days if corneal re-epithelialization has not occurred.

Infants, Children, and Adolescents

2 drops in affected eye(s) every 15 minutes for 6 hours then every 30 minutes for the remainder of the first day. For the second day, 2 drops every 1 hour. For days 3 to 14, 2 drops every 4 hours. Treatment may be continued after 14 days if corneal re-epithelialization has not occurred.

Neonates

2 drops in affected eye(s) every 15 minutes for 6 hours then every 30 minutes for the remainder of the first day. For the second day, 2 drops every 1 hour. For days 3 to 14, 2 drops every 4 hours. Treatment may be continued after 14 days if corneal re-epithelialization has not occurred.

500 mg PO every 12 hours for 60 days after exposure. Ciprofloxacin is recommended as one of the preferred therapies for postexposure prophylaxis.

Infants, Children, and Adolescents

15 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) for 60 days after exposure. Ciprofloxacin is recommended as one of the preferred therapies for postexposure prophylaxis.

Term Neonates

15 mg/kg/dose PO every 12 hours for 60 days after exposure. Ciprofloxacin is recommended as one of the preferred therapies for postexposure prophylaxis.

Premature neonates 32 to 37 weeks gestational age

10 mg/kg/dose PO every 12 hours for 60 days after exposure is recommended in guidelines. 15 mg/kg/dose PO every 12 hours is the general FDA-approved pediatric dosage. Ciprofloxacin is recommended as one of the preferred therapies for postexposure prophylaxis.

Intravenous dosage

Adults

400 mg IV every 12 hours for 60 days after exposure. Ciprofloxacin is recommended as one of the preferred therapies for postexposure prophylaxis.

Infants, Children, and Adolescents

10 mg/kg/dose IV every 12 hours (Max: 400 mg/dose) for 60 days after exposure. Ciprofloxacin is recommended as one of the preferred therapies for postexposure prophylaxis.

Neonates

10 mg/kg/dose IV every 12 hours for 60 days after exposure. Ciprofloxacin is recommended as one of the preferred therapies for postexposure prophylaxis.

For the treatment of plague infection.

For treatment in a contained casualty setting.

Intravenous dosage

Adults

400 mg IV every 12 hours for 10 days is recommended in guidelines. The FDA-approved dosage is 400 mg IV every 8 to 12 hours for 14 days. Begin treatment as soon as possible after suspected or confirmed exposure. Switch to oral antibiotic therapy when clinically indicated. Ciprofloxacin is recommended if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin or gentamicin. Women who are breast-feeding should be treated with the same antibiotic as the infant.

Infants, Children, and Adolescents

15 mg/kg/dose IV every 12 hours (Max: 400 mg/dose) for 10 days is recommended in guidelines. The FDA-approved dosage is 10 mg/kg/dose IV every 8 to 12 hours (Max: 400 mg/dose) for 10 to 21 days. Begin treatment as soon as possible after suspected or confirmed exposure. Switch to oral antibiotic therapy when clinically indicated. Ciprofloxacin is recommended if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin or gentamicin.

Neonates

15 mg/kg/dose IV every 12 hours for 10 days is recommended in guidelines. The FDA-approved dosage is 10 mg/kg/dose IV every 8 to 12 hours for 10 to 21 days. Begin treatment as soon as possible after suspected or confirmed exposure. Switch to oral antibiotic therapy when clinically indicated. Ciprofloxacin is recommended if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin or gentamicin.

For treatment in a mass casualty setting.

Oral dosage

Adults

500 mg PO every 12 hours for 10 days is recommended in guidelines. The FDA-approved dosage is 500 to 750 mg PO every 12 hours for 14 days. Begin treatment as soon as possible after suspected or confirmed exposure. Tetracyclines or a quinolone are the treatments of choice for plague in the mass casualty setting. Women who are breast-feeding should be treated with the same antibiotic as the infant.

Infants, Children, and Adolescents

20 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) for 10 days is recommended in guidelines. The FDA-approved dosage is 15 mg/kg/dose PO every 8 to 12 hours (Max: 500 mg/dose) for 10 to 21 days. Begin treatment as soon as possible after suspected or confirmed exposure. Tetracyclines or a quinolone are the treatments of choice for plague in the mass casualty setting.

Neonates

20 mg/kg/dose PO every 12 hours for 10 days is recommended in guidelines. The FDA-approved dosage is 15 mg/kg/dose PO every 8 to 12 hours for 10 to 21 days. Begin treatment as soon as possible after suspected or confirmed exposure. Tetracyclines or a quinolone are the treatments of choice for plague in the mass casualty setting.

For plague prophylaxis following exposure to Yersinia pestis.

Oral dosage

Adults

500 mg PO every 12 hours for 7 days is recommended in guidelines. The FDA-approved dosage is 500 to 750 mg PO every 12 hours for 14 days. Begin treatment as soon as possible after suspected or confirmed exposure. Tetracyclines or a quinolone are the treatments of choice for plague prophylaxis. Women who are breast-feeding should be treated with the same antibiotic as the infant.

Infants, Children, and Adolescents

20 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) for 7 days is recommended in guidelines. The FDA-approved dosage is 15 mg/kg/dose PO every 8 to 12 hours (Max: 500 mg/dose) for 10 to 21 days. Begin treatment as soon as possible after suspected or confirmed exposure. Tetracyclines or a quinolone are the treatments of choice for plague prophylaxis.

Neonates

20 mg/kg/dose PO every 12 hours for 7 days is recommended in guidelines. The FDA-approved dosage is 15 mg/kg/dose PO every 8 to 12 hours for 10 to 21 days. Begin treatment as soon as possible after suspected or confirmed exposure. Tetracyclines or a quinolone are the treatments of choice for plague prophylaxis.

For the treatment of acute otitis externa due to susceptible isolates of Pseudomonas aeruginosa or Staphylococcus aureus.

500 mg PO every 12 hour for 10 days. 15 mg/kg/day PO in divided doses for 5 to 7 days is recommended by the World Health Organization (WHO) for uncomplicated disease. Three-day courses may also be effective.

Infants†, Children†, and Adolescents†

15 mg/kg/day PO in divided doses (Max: 500 mg/dose) for 5 to 7 days is recommended by the World Health Organization (WHO) for uncomplicated disease. Three-day courses may also be effective. Doses of 20 mg/kg/day PO in 2 divided doses have also been used.

Intravenous dosage†

Adults

15 mg/kg/day IV in divided doses for 10 to 14 days is recommended by the World Health Organization (WHO) for severe disease.

Infants, Children, and Adolescents

15 mg/kg/day IV in divided doses (Max: 400 mg/dose) for 10 to 14 days is recommended by the World Health Organization (WHO) for severe disease. Doses of 10 to 20 mg/kg/day IV in 2 divided doses have also been used.

For the treatment of shigellosis.

Oral dosage

Adults

500 mg PO every 12 hours for 5 to 7 days. The World Health Organization (WHO) and the Infectious Diseases Society of America (IDSA) recommend treating for 3 days. 500 to 750 mg PO every 12 hours is recommended by the HIV guidelines. Treat for 7 to 10 days or extend therapy to at least 14 days with bacteremia. Recurrent infection may require treating for up to 6 weeks.

Adolescents†

15 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) for 3 days is recommended by the World Health Organization (WHO). 500 to 750 mg PO every 12 hours is recommended by the HIV guidelines. Treat for 7 to 10 days or extend therapy to at least 14 days with bacteremia. Recurrent infection may require treating for up to 6 weeks.

Infants† and Children†

15 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) for 3 days is recommended by the World Health Organization (WHO).

Intravenous dosage†

Adults

400 mg IV every 12 hours is recommended by guidelines for HIV-infected patients. Treat for 7 to 10 days or extend therapy to at least 14 days with bacteremia. Recurrent infection may require treating for up to 6 weeks.

Adolescents

400 mg IV every 12 hours is recommended by guidelines for HIV-infected patients. Treat for 7 to 10 days or extend therapy to at least 14 days with bacteremia. Recurrent infection may require treating for up to 6 weeks.

For the treatment of campylobacteriosis.

Oral dosage

Adults

500 mg PO every 12 hours for 5 to 7 days. 500 to 750 mg PO every 12 hours is recommended by guidelines for HIV-infected patients. Add an aminoglycoside for bacteremia. Treat for 7 to 10 days in mild-to-moderate disease and at least 14 days for bacteremia. Patients with recurrent bacteremia may require treatment for 2 to 6 weeks.

Adolescents†

500 to 750 mg PO every 12 hours is recommended by guidelines for HIV-infected patients. Add an aminoglycoside for bacteremia. Treat for 7 to 10 days in mild-to-moderate disease and at least 14 days for bacteremia. Patients with recurrent bacteremia may require treatment for 2 to 6 weeks.

Intravenous dosage†

Adults

400 mg IV every 12 hours is recommended by guidelines for HIV-infected patients. Add an aminoglycoside for bacteremia. Treat for 7 to 10 days in mild-to-moderate disease and at least 14 days for bacteremia. Patients with recurrent bacteremia may require treatment for 2 to 6 weeks.

Adolescents

400 mg IV every 12 hours is recommended by guidelines for HIV-infected patients. Add an aminoglycoside for bacteremia. Treat for 7 to 10 days in mild-to-moderate disease and at least 14 days for bacteremia. Patients with recurrent bacteremia may require treatment for 2 to 6 weeks.

For the treatment of acute systemic brucellosis† caused by Brucella melitensis.

Oral dosage

Adults

500 mg PO every 8 to 12 hours for 6 to 12 weeks or 750 mg PO every 8 hours for 6 to 8 weeks.

For the treatment of chancroid† due to Haemophilus ducreyi.

Oral dosage

Adults

The CDC recommends 500 mg PO twice daily for 3 days. Complicated or severe infections may require prolonged therapy. A longer course of therapy may be required in HIV-infected patients and uncircumcised men. Worldwide, isolates with intermediate resistance have been reported; however, data are limited regarding prevalence. The CDC suggests alternate agents should be used in pregnant and lactating women with chancroid.

Adolescents

500 mg PO twice daily for 3 days. A longer course of therapy may be required in HIV-infected patients and uncircumcised males. Worldwide, isolates with intermediate resistance have been reported; however, data are limited regarding prevalence. The CDC suggests alternate agents should be used in pregnant and lactating women with chancroid.

For the treatment of granuloma inguinale† (Donovanosis) caused by Klebsiella granulomatis.

Oral dosage

Adults

As an alternative, the CDC recommends 750 mg PO twice daily for 3 weeks and until all lesions have completely healed. The addition of an aminoglycoside, such as gentamicin, should be considered if lesions do not respond within the first few days of therapy or if the patient also has HIV infection. For pregnant and lactating patients, use erythromycin or azithromycin.

Adolescents

750 mg PO twice daily for at least 3 weeks and until all lesions have healed is recommended as an alternative to azithromycin. Consider the addition of an aminoglycoside, such as gentamicin, if lesions do not respond within the first few days of therapy or if the patient also has HIV infection. For pregnant and lactating patients, use erythromycin or azithromycin.

For the treatment of Neisseria meningitidis† nasal carrier state (i.e., for meningococcal infection prophylaxis†).

Oral dosage

Adults

Limited data suggest that 500 mg PO every 12 hours for 5 days eliminates meningococcus from the nasopharynx for up to 13 days. 500 to 750 mg PO as a single dose or 250 mg PO twice daily have also been used.

Infants, Children, and Adolescents

20 mg/kg/dose PO as a single dose (Max: 500 mg/dose) in high-risk contacts. Not routinely recommended in pediatrics, but may be justified after assessment of the risks and benefits for individual patients.

For the treatment of dental infection†, including dentoalveolar infection† and periodontitis†.

For adult chronic periodontitis† after scaling and root planing.

Oral dosage

Adults

500 mg PO twice daily for 8 days.

For adult refractory chronic periodontitis† in combination with metronidazole after scaling and root planing in beta-lactam allergic patients.

Oral dosage

Adults

500 mg PO twice daily in combination with metronidazole for 8 days.

For the treatment of anthrax†.

For the treatment of cutaneous anthrax.

Oral dosage

Adults

500 mg PO every 12 hours is a preferred therapy for cutaneous anthrax infection. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, treat for a total duration of 60 days. Ciprofloxacin is a preferred therapy for cutaneous anthrax infection.

Infants, Children, and Adolescents

15 mg/kg/dose PO every 12 hours (Max: 500 mg/dose). Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, treat for a total duration of 60 days. Ciprofloxacin is the preferred therapy for cutaneous anthrax infection.

Term Neonates

15 mg/kg/dose PO every 12 hours. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, treat for a total duration of 60 days. Ciprofloxacin is the preferred therapy for cutaneous anthrax infection.

Premature Neonates 32 to 37 weeks gestational age

10 mg/kg/dose PO every 12 hours. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, treat for a total duration of 60 days. Ciprofloxacin is the preferred therapy for cutaneous anthrax infection.

For the treatment of systemic anthrax infection.

Intravenous dosage

Adults

400 mg IV every 8 hours. For systemic infection in which meningitis can be excluded, IV treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, IV treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ciprofloxacin, in combination with appropriate antimicrobial therapy, is a preferred therapy for systemic anthrax infection. For systemic infection without CNS involvement, dual combination IV therapy with ciprofloxacin and a protein synthesis inhibitor (i.e., clindamycin, linezolid, doxycycline) or rifampin is recommended. For documented or suspected CNS infection, triple IV therapy with ciprofloxacin, a beta-lactam/glycopeptide, and a protein synthesis inhibitor (i.e., linezolid, clindamycin, chloramphenicol) or rifampin is recommended.

Infants, Children, and Adolescents

10 mg/kg/dose IV every 8 hours (Max: 400 mg/dose). For systemic infection in which meningitis can be excluded, treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ciprofloxacin, in combination with appropriate antimicrobial therapy, is a preferred therapy for systemic anthrax infection. For systemic infection without CNS involvement, dual combination IV therapy with ciprofloxacin and a protein synthesis inhibitor (e.g., clindamycin, linezolid, doxycycline) is recommended. For documented or suspected CNS infection, triple IV therapy with ciprofloxacin, a beta-lactam/glycopeptide, and a protein synthesis inhibitor (e.g., linezolid, clindamycin) is recommended.

Term Neonates

15 mg/kg/dose IV every 12 hours. For systemic infection in which meningitis can be excluded, treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ciprofloxacin, in combination with appropriate antimicrobial therapy, is a preferred therapy for systemic anthrax infection. For systemic infection without CNS involvement, dual combination IV therapy with ciprofloxacin and a protein synthesis inhibitor (e.g., clindamycin, linezolid, doxycycline) is recommended. For documented or suspected CNS infection, triple IV therapy with ciprofloxacin, a beta-lactam/glycopeptide, and a protein synthesis inhibitor (e.g., linezolid, clindamycin) is recommended.

Premature Neonates 32 to 37 weeks gestational age

10 mg/kg/dose IV every 12 hours. For systemic infection in which meningitis can be excluded, treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases. Ciprofloxacin, in combination with appropriate antimicrobial therapy, is a preferred therapy for systemic anthrax infection. For systemic infection without CNS involvement, dual combination IV therapy with ciprofloxacin and a protein synthesis inhibitor (e.g., clindamycin, linezolid, doxycycline) is recommended. For documented or suspected CNS infection, triple IV therapy with ciprofloxacin, a beta-lactam/glycopeptide, and a protein synthesis inhibitor (e.g., linezolid, clindamycin) is recommended.

Oral dosage

Infants, Children, and Adolescents

15 mg/kg/dose PO every 12 hours (Max: 500 mg/dose). Treatment should continue to complete a treatment course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required. Ciprofloxacin, in combination with a protein synthesis inhibitor (e.g., clindamycin, doxycycline, linezolid), is recommended as the preferred oral follow-up combination therapy for severe anthrax (non-CNS infection).

Term Neonates

15 mg/kg/dose PO every 12 hours. Treatment should continue to complete a treatment course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required. Ciprofloxacin, in combination with a protein synthesis inhibitor (e.g., clindamycin, doxycycline, linezolid), is recommended as the preferred oral follow-up combination therapy for severe anthrax (non-CNS infection).

Premature neonates 32 to 37 weeks gestational age

10 mg/kg/dose PO every 12 hours. Treatment should continue to complete a treatment course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required. Ciprofloxacin, in combination with a protein synthesis inhibitor (e.g., clindamycin, doxycycline, linezolid), is recommended as the preferred oral follow-up combination therapy for severe anthrax (non-CNS infection).

For the treatment of cholera†.

Oral dosage

Adults

1 g PO as a single dose per clinical practice guidelines.

Children and Adolescents

20 mg/kg/dose PO as a single dose (Max: 750 mg/dose) has been studied. Ciprofloxacin was compared to erythromycin in a randomized, open label, controlled trial in patients age 2 to 15 years with cholera. Ciprofloxacin as a single dose (n = 90) was shown to have similar or better efficacy than standard 3-day, 12-dose erythromycin therapy (n = 90). However, ciprofloxacin was less effective in eradicating Vibrio cholerae from stool. In a study comparing single-dose ciprofloxacin (n = 90) to single-dose azithromycin (n = 89) in children age 2 to 12 years, azithromycin was superior with a clinical success rate of 94.5% as compared to a 70.6% success rate for ciprofloxacin.

For the treatment of tularemia† infection or for postexposure tularemia prophylaxis†.

For an individual patient† or in a contained casualty setting†. NOTE: Streptomycin is the drug of choice to treat tularemia in most patients; gentamicin is the preferred agent in pregnant women.

Intravenous dosage

Adults

400 mg IV every 12 hours for 10 days. Patients should be switched to oral antibiotic therapy when clinically indicated. The risk of serious infection after tularemia exposure supports the use of ciprofloxacin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin. Women who are breast-feeding should be treated with the same antibiotic as the infant.

Infants, Children, and Adolescents

15 mg/kg/dose IV every 12 hours (Max: 400 mg/dose) for 10 days as alternative therapy. Switch to oral antibiotic therapy when clinically indicated. Ciprofloxacin is recommended if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin or gentamicin.

Neonates

15 mg/kg/dose IV every 12 hours for 10 days as alternative therapy. Switch to oral antibiotic therapy when clinically indicated. Ciprofloxacin is recommended if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin or gentamicin.

For a mass casualty setting† and for tularemia prophylaxis† after exposure to Francisella tularensis. NOTE: Doxycycline is the treatment of choice for tularemia in the most patients. Ciprofloxacin is the drug of choice for pregnant women; if ciprofloxacin is contraindicated, doxycycline should be used.

Oral dosage

Adults

500 PO every 12 hours for 14 days may be reasonable for mild to moderate illness. The risk of serious infection after tularemia exposure supports the use of ciprofloxacin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of doxycycline.

Infants, Children, and Adolescents

15 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) for 14 days.

Neonates

15 mg/kg/dose PO every 12 hours for 14 days.

For use as maintenance treatment of melioidosis† due to Burkholderia pseudomallei†.

Oral dosage

Adults

10 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) with or without azithromycin for up to 20 weeks has been studied.

Adolescents

10 mg/kg/dose PO every 12 hours (Max: 500 mg/dose) with or without azithromycin for up to 20 weeks has been studied.

For surgical infection prophylaxis†.

Intravenous dosage

Adults

400 mg IV as a single preoperative dose for procedures involving lower urinary tract instrumentation or as an alternative option as part of combination therapy in gastrointestinal, transplantation, hysterectomy, urogynecology, and other urologic procedures. Doses should be administered within 120 minutes prior to the surgical incision. No redosing is recommended; the duration of prophylaxis should be less than 24 hours for most procedures.

Infants, Children, and Adolescents

10 mg/kg/dose IV as a single dose (Max: 400 mg/dose) within 120 minutes prior to the surgical incision. No redosing is recommended. Quinolones are not considered drugs of first choice in pediatric populations due to the incidence of adverse reactions. Quinolones may be used as an alternative option in a number of surgical procedures including several gastrointestinal procedures, urologic procedures, and transplantations. Generally, they are used as part of combination therapy except for procedures involving lower urinary tract instrumentation.

For the treatment of acute pulmonary exacerbations in cystic fibrosis† (CF) patients.

Intravenous dosage

Adults

400 mg IV every 8 hours is recommended as part of combination therapy for Pseudomonas aeruginosa. Current dosage recommendations may be suboptimal to achieve an adequate AUC:MIC ratio with P. aeruginosa MICs exceeding 0.125 mg/L.

Infants, Children, and Adolescents

10 mg/kg/dose IV every 8 hours (Max: 1.2 g/day) is the most commonly recommended dosage, often as part of combination therapy for Pseudomonas aeruginosa. Limited pharmacodynamic data suggest current dosage strategies may be suboptimal in achieving an adequate AUC:MIC ratio with P. aeruginosa isolates with MICs exceeding 0.125 mg/L ; however, data supporting higher dosages is not available.

Oral dosage

Adults

750 mg PO every 12 hours is recommended as part of combination therapy for Pseudomonas aeruginosa. Current dosage recommendations may be suboptimal to achieve an adequate AUC:MIC ratio with P. aeruginosa MICs exceeding 0.125 mg/L.

Infants, Children, and Adolescents

20 mg/kg/dose PO every 12 hours (Max: 2 g/day) is the most commonly recommended dosage, often as part of combination therapy for Pseudomonas aeruginosa. Limited pharmacodynamic data suggest current dosage strategies may be suboptimal in achieving an adequate AUC:MIC ratio with P. aeruginosa isolates with MICs exceeding 0.125 mg/L ; however, data supporting higher dosages is not available.

For bacterial infection prophylaxis† in patients with cirrhosis and GI bleeding.

Intravenous dosage

Adults

Short-term use of 400 mg IV every 12 hours for 7 days as an alternative to norfloxacin has been recommended, beginning immediately after endoscopy in patients with or without ascites.

Oral dosage

Adults

Short-term use of 500 mg PO every 12 hours for 7 days has been studied, beginning immediately after endoscopy in patients with or without ascites. Long-term prophylaxis of 500 mg PO daily in patients with advanced cirrhosis, particularly those awaiting liver transplant has also been recommended.

For the treatment of CAPD-associated peritonitis†.

For the treatment of exit-site† and tunnel infections† in CAPD patients.

Oral dosage

Adults

250 mg PO every 12 hours continued until the exit site appears completely normal with a 2 week minimum duration and 3 weeks for infections due to P. aeruginosa.

Infants, Children, and Adolescents

10 to 15 mg/kg/dose PO every 24 hours (Max: 500 mg/dose). Treat for a minimum of 2 weeks and for at least 7 days after complete resolution of the infection for exit site infections. P. aeruginosa may require 3 weeks of therapy. Treat for 2 to 4 weeks for tunnel infections.

Intraperitoneal dosage

Adults

50 mg/L of peritoneal dialysate as a loading dose followed by a maintenance dose of 25 mg/L of peritoneal dialysate. For the loading dose, allow a dwell time of at least 6 hours; after the loading dose, all other exchanges should contain the maintenance dose. Treat for 2 to 3 weeks depending on infecting organism and the patient's clinical status.

Infants, Children, and Adolescents

50 mg/L of peritoneal dialysate as a loading dose followed by a maintenance dose of 25 mg/L of peritoneal dialysate. For the loading dose, allow a dwell time of 3 to 6 hours; after the loading dose, all other exchanges should contain the maintenance dose. Treat for 2 to 3 weeks depending on infecting organism and the patient's clinical status.

For the treatment of infective endocarditis†.

Intravenous dosage

Adults

400 mg IV every 12 hours as alternative for 4 weeks for native valve endocarditis and for 6 weeks for prosthetic valve endocarditis due to HACEK organisms in patients unable to tolerate cephalosporin or ampicillin therapy.

Children and Adolescents

10 to 15 mg/kg/dose IV every 12 hours (Max: 400 mg/dose) as alternative for 4 to 6 weeks in combination with vancomycin and gentamicin for culture-negative native valve endocarditis in patients unable to tolerate penicillins.

Oral dosage

Adults

500 mg PO every 12 hours as alternative for 4 weeks for native valve endocarditis and for 6 weeks for prosthetic valve endocarditis due to HACEK organisms in patients unable to tolerate cephalosporin or ampicillin therapy.

Children and Adolescents

10 to 15 mg/kg/dose PO every 12 hours (Max: 750 mg/dose) as alternative for 4 to 6 weeks in combination with vancomycin and gentamicin for culture-negative native valve endocarditis in patients unable to tolerate penicillins.

For the treatment of Mycobacterium avium complex infection† (MAC) in HIV-infected patients.

Oral dosage

Infants and Children

10 to 15 mg/kg/dose PO every 12 hours (Max: 750 mg/dose) is recommended by the CDC as part of a 3 or 4 drug regimen.

For the treatment of salmonellosis†.

Oral dosage

Adults

500 mg PO every 12 hours for 5 to 7 days is recommended by the Infectious Diseases Society of America (IDSA). 500 to 750 mg PO every 12 hours is recommended by guidelines for HIV-infected patients. For patients with CD4 count of 200 cells/mm3 or higher, the duration of therapy is 7 to 14 days for patients without bacteremia and 14 days for patients with bacteremia. A longer duration may be necessary with persistent or complicated infections. For patients with CD4 count less than 200 cells/mm3, the duration of therapy is 2 to 6 weeks with or without bacteremia. The role of long term secondary prophylaxis is not well established, but may be considered for patients with recurrent infection and in patients with CD4 count less than 200 cells/mm3 with severe diarrhea.

Adolescents

500 to 750 mg PO every 12 hours is recommended by guidelines for HIV-infected patients. For patients with CD4 count of 200 cells/mm3 or higher, the duration of therapy is 7 to 14 days for patients without bacteremia and 14 days for patients with bacteremia. A longer duration may be necessary with persistent or complicated infections. For patients with CD4 count less than 200 cells/mm3, the duration of therapy is 2 to 6 weeks with or without bacteremia. The role of long term secondary prophylaxis is not well established, but may be considered for patients with recurrent infection and in patients with CD4 count less than 200 cells/mm3 with severe diarrhea.

Intravenous dosage

Adults

400 mg IV every 12 hours is recommended by guidelines for HIV-infected patients. For patients with CD4 count of 200 cells/mm3 or higher, the duration of therapy is 7 to 14 days for patients without bacteremia and 14 days for patients with bacteremia. A longer duration may be necessary with persistent or complicated infections. For patients with CD4 count less than 200 cells/mm3, the duration of therapy is 2 to 6 weeks with or without bacteremia. The role of long term secondary prophylaxis is not well established, but may be considered for patients with recurrent infection and in patients with CD4 count less than 200 cells/mm3 with severe diarrhea.

Adolescents

400 mg IV every 12 hours is recommended by guidelines for HIV-infected patients. For patients with CD4 count of 200 cells/mm3 or higher, the duration of therapy is 7 to 14 days for patients without bacteremia and 14 days for patients with bacteremia. A longer duration may be necessary with persistent or complicated infections. For patients with CD4 count less than 200 cells/mm3, the duration of therapy is 2 to 6 weeks with or without bacteremia. The role of long term secondary prophylaxis is not well established, but may be considered for patients with recurrent infection and in patients with CD4 count less than 200 cells/mm3 with severe diarrhea.

For the treatment of moderate or severe traveler's diarrhea†.

Oral dosage

Adults

750 mg PO as a single dose or 500 mg PO once daily for 3 days. If symptoms are not resolved after single dose, continue daily dosing for up to 3 days. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.

Infants, Children, and Adolescents

20 to 30 mg/kg/day PO in 1 or 2 divided doses as an alternative therapy; the recommended adult dosage is 750 mg PO as a single dose or 500 mg PO once daily for 3 days. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.

For the treatment of isosporiasis† (Isospora belli) in HIV-infected patients.

Oral dosage

Adults

500 mg PO every 12 hours for 7 days is recommended by the HIV guidelines as a second line alternative. Secondary prophylaxis with 500 mg PO three times weekly is recommended after treatment in patients with CD4 count less than 200 cells/mm3. Secondary prophylaxis should continue until CD4 count is 200 cells/mm3 or more for at least 6 months after antiretroviral therapy has been initiated and there is no further evidence of I. belli infection.

Adolescents

500 mg PO every 12 hours for 7 days is recommended by the HIV guidelines as a second line alternative. Secondary prophylaxis with 500 mg PO three times weekly is recommended after treatment in patients with CD4 count less than 200 cells/mm3. Secondary prophylaxis should continue until CD4 count is 200 cells/mm3 or more for at least 6 months after antiretroviral therapy has been initiated and there is no further evidence of I. belli infection.

For the treatment of sepsis†.

Intravenous dosage

Adults

600 mg IV every 12 hours. Start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

6 to 11 months: 45 mg/kg/day PO or 30 mg/kg/day IV; 120 drops/eye/day of ophthalmic solution; 12 mg/ear for otic suspension. Safety and efficacy of other formulations have not been established.1 to 5 months: 45 mg/kg/day PO or 30 mg/kg/day IV; 120 drops/eye/day of ophthalmic solution. Safety and efficacy of other formulations have not been established.

Neonates

45 mg/kg/day PO or 30 mg/kg/day IV; 120 drops/eye/day of ophthalmic solution. Safety and efficacy of other formulations have not been established.

DOSING CONSIDERATIONS

Hepatic Impairment

In studies in patients with stable chronic cirrhosis, no significant changes in pharmacokinetics have been observed; it appears no dosage adjustment is needed. Ciprofloxacin has not been studied in patients with acute hepatic insufficiency.

Renal Impairment

AdultsFDA-labeled renal dosing adjustment recommendations: CrCl more than 50 mL/minute: No dosage adjustment needed.CrCl 30 to 50 mL/minute: For oral administration of the regular tablets and suspension, the recommended dosage is 250 to 500 mg PO every 12 hours; doses of 750 mg may also be used, but with careful monitoring. No dosage adjustment is recommended for the IV formulation or extended-release tablets.CrCl 5 to 29 mL/minute: For the regular tablets and suspension, 250 to 500 mg PO every 18 hours; doses of 750 mg may also be used, but with careful monitoring. For the IV formulation 200 to 400 mg IV every 18 to 24 hours. For the extended-release tablets, 500 mg PO every 24 hours.

Other renal dosing adjustment recommendations: CrCl more than 50 mL/minute: No dosage adjustment needed.CrCl 10 to 50 mL/minute: Administer 50 to 75% of the regular dose.CrCl less than 10 mL/minute: Administer 50% of the regular dose.

Pediatric patientsThe following dose adjustments are based on a usual pediatric dose of 10 to 15 mg/kg/dose every 12 hours:GFR 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.GFR 10 to 29 mL/minute/1.73 m2: 10 to 15 mg/kg/dose IV/PO every 18 hours.GFR less than 10 mL/minute/1.73 m2: 10 to 15 mg/kg/dose IV/PO every 24 hours.

Intermittent hemodialysisAdultsFor the regular tablets and suspension, the FDA-labeled adjustment is 250 to 500 mg PO every 24 hours; doses of 750 mg may also be used, but with careful monitoring. Other recommendations suggest 250 mg PO every 12 hours. For the IV formulation, the FDA-labeled dosage adjustment is 200 to 400 mg IV every 18 to 24 hours. Other recommendations suggest 200 mg IV every 12 hours. For the extended-release tablets, 500 mg PO every 24 hours. Administer the dose after hemodialysis on dialysis days.

Peritoneal dialysisAdultsFor the regular tablets and suspension, the FDA-labeled adjustment is 250 to 500 mg PO every 24 hours; doses of 750 mg may also be used, but with careful monitoring. Other recommendations suggest 250 mg PO every 8 hours. For the IV formulation, the FDA-labeled adjustment is 200 to 400 mg IV every 18 to 24 hours. Other recommendations suggest 200 mg IV every 8 hours. For the extended-release tablets, 500 mg PO every 24 hours.

Pediatric patients10 to 15 mg/kg/dose IV/PO every 24 hours.

ADMINISTRATION

Oral Administration

NOTE: Ciprofloxacin extended-release tablets and immediate-release tablets are NOT interchangeable.Ciprofloxacin may be administered with or without meals. Administer at least 2 hours before or 6 hours after any of the following: magnesium/aluminum antacids, sucralfate, didanosine chewable/buffered tablets or pediatric powder for oral solution, or other products containing calcium, iron, or zinc. Do not administer with dairy products or calcium-fortified juices alone; however, ciprofloxacin may be taken with a meal that contains these products.

Oral Solid Formulations

Extended-release tablets: Swallow whole; do not split, crush, or chew.

Oral Liquid Formulations

ReconstitutionPour the microcapsules from the small bottle into the large bottle of supplied diluent. Do not add water to the suspension. Close the large bottle and shake vigorously for about 15 seconds. The 5% ciprofloxacin oral suspension will contain 250 mg ciprofloxacin per 5 mL and the 10% suspension will contain 500 mg ciprofloxacin per 5 mL. Each bottle will contain 100 mL total volume.Storage: The reconstituted suspension is stable for 14 days when stored below 30 degrees C (86 degrees F). Do not freeze.

AdministrationShake vigorously for about 15 seconds before each use. Use a calibrated oral syringe or other calibrated oral device to measure accurate dosage. Instruct patient not to chew microcapsules when taking the dose.Do not administer ciprofloxacin oral suspension through a feeding tube due to its physical characteristics.

Concentrate vialsWithdraw appropriate dose (10 mg/mL concentration) and dilute with a compatible solution to a concentration of 1 to 2 mg/mL.Compatible solutions include: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Sterile Water for Injection, 10% Dextrose for Injection, 5% Dextrose and 0.225% Sodium Chloride for Injection, 5% Dextrose and 0.45% Sodium Chloride for Injection, and Lactated Ringer's for Injection.Storage: All diluted infusions (concentration 0.5 to 2 mg/mL) may be stored for up to 14 days at either room temperature or under refrigeration. Do not freeze.

Prefilled flexible infusion containersAlready diluted in 5% dextrose to a concentration of 2 mg/mL; no further dilution is necessary. Containers are latex-free.

Intermittent IV InfusionInfuse appropriate dose over 60 minutes via a large vein to minimize discomfort and reduce the risk of venous irritation. Shorter infusions (30 minutes or less) or administration via a small vein increases incidence of local reactions.Infusion may occur via direct infusion or via Y-site. If Y-site administration is chosen, it is advisable to discontinue the administration of any other parenteral drug products during the infusion. If this is not possible, then ciprofloxacin and the other medication should be given separately (i.e., not at the same time through the Y-site).

Ophthalmic Administration

Commercially available ophthalmic solutions are not for injection subconjunctivally or into the anterior chamber of the eye.Apply topically to the eye taking care to avoid contamination. For ophthalmic use only.Instruct patient on proper instillation of eye solution or ointment.Do not to touch the tip of the dropper to the eye, fingertips, or other surface.

Otic Administration

Otic Solution (Cetraxal)Commercially available otic solutions are not for injection, inhalation, or topical ophthalmic use.Instruct patient on proper instillation of otic solution.Warm the container in the hands for at least 1 minute prior to administration to minimize dizziness that may result from the instillation of a cold solution into the ear canal.The patient should lie with the affected ear upward for instillation and continue to maintain this position for at least 1 minute after instillation.Instill the contents of 1 single use container (0.25 mL) into the affected ear.Discard used container.

Otic Suspension (Otiprio)Gather all materials needed:Acute otitis externa: one vial of ciprofloxacin otic suspension; one 1 mL luer lock syringe for each affected ear; one 18 to 21 gauge preparation needle for each affected ear; one 20 to 24 gauge, 1.5 inch blunt, flexible administration needle for each affected ear; and alcohol pads. Ice pack and drape to keep the otic suspension vial cold is optional.Otitis media with effusion: one vial of ciprofloxacin otic suspension; two 1 mL luer lock syringes; two 18 to 21 gauge preparation needles; two 20 to 24 gauge, 2 to 3 inch blunt, flexible administration needles; and alcohol pads. Ice pack and drape to keep the otic suspension vial cold is optional.Ciprofloxacin suspension MUST be kept cold during preparation; if the suspension thickens during preparation, place vial back in refrigeration.Hold vial by the aluminum seal while shaking to prevent gelation. Shake the vial for 5 to 8 seconds to mix well until a visually homogenous suspension is obtained.Withdraw 0.3 mL of the suspension into the 1 mL syringe using an 18 to 21 gauge needle.Replace the needle with a 20 to 24 gauge, 1.5 inch (acute otitis externa) or 2 to 3 inch (otitis media with effusion) blunt, flexible needle to be used for administration.Prime the needle leaving a dose of 0.2 mL (acute otitis externa) or 0.1 mL (otitis media with effusion).Using a different syringe, but the same vial, prepare a second syringe for the other ear (if needed) and dispose of the vial.Storage: Syringes can be kept at room temperature or in the refrigerator for up to 3 hours prior to administration. Keep syringes on their side.

CONTRAINDICATIONS / PRECAUTIONS

Viral infection

Ciprofloxacin does not treat viral infection (e.g., common cold). Prescribing ciprofloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Patients should be told to complete the full course of treatment, even if they feel better earlier. Antibiotic therapy can result in superinfection or suprainfection with non susceptible organisms. Overgrowth of Candida can occur with ciprofloxacin therapy. Patients should be monitored closely during therapy.

Quinolone hypersensitivity

Ciprofloxacin should not be used in patients with quinolone hypersensitivity. Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and pruritus. Severe hypersensitivity reactions characterized by rash, fever, eosinophilia, angioedema, or other symptoms of an allergic reaction have been reported in patients receiving quinolone antibiotics. Ciprofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should be administered as indicated.

Systemic quinolones have been associated with disabling and potentially irreversible serious adverse reactions such as tendinopathy, including tendinitis and tendon rupture requiring surgical repair or resulting in prolonged disability. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Because of this risk for serious and potentially permanent side effects, quinolones should only be used for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis in cases where alternative treatment options cannot be used. Discontinue quinolones at the first sign of tendon inflammation or tendon pain as these are symptoms that may precede rupture of the tendon. Avoid quinolone use in patients with a history of tendon disorders or tendon rupture. Tendon rupture typically involves the Achilles tendon; however, ruptures of the hand, shoulder, biceps, thumb, and other tendons have also been reported. Tendinitis and tendon rupture can occur bilaterally. Rupture can occur during therapy or up to a few months after therapy has been stopped. The risk of tendon rupture is further increased in older adults (more than 60 years of age), those receiving concomitant corticosteroid therapy, and in organ transplant recipients (including kidney, heart, and lung transplants). Reasons for tendon ruptures also include physical activity or exercise, kidney failure, or tendon problems in the past. If patients experience tendon inflammation or pain, they should rest and refrain from exercise until the diagnosis of tendonitis or tendon rupture has been confidently excluded.

Ciprofloxacin should be used cautiously in patients with cardiac arrhythmias or other cardiac disease that predisposes to cardiac arrhythmias. Fluoroquinolones have the potential to cause QT prolongation and possibly torsade de pointes (TdP) by blocking human cardiac potassium (K+) channel currents. The potency of this blockade varies among the quinolones. Ciprofloxacin appears to block human cardiac K+ channels with a lower potency than other quinolones such as levofloxacin. Based on cardiac studies, clinical trials, and postmarketing evaluations, the overall risk for TdP with ciprofloxacin is lower compared with other quinolones such as levofloxacin and moxifloxacin. Rare cases of TdP during postmarketing experience have been reported with ciprofloxacin; however, no cardiovascular morbidity or deaths have been reported due to ciprofloxacin-associated QT prolongation. The unmonitored use of quinolones in patients with a stable ischemic heart and preserved left ventricular function is likely safe and the risk of QT prolongation and TdP is low. However, avoid the unmonitored use of quinolones in patients with known QT prolongation, patients with ongoing proarrhythmic conditions that may increase the risk of developing TdP (e.g., uncorrected hypokalemia or hypomagnesemia, significant bradycardia, congestive heart failure, acute myocardial ischemia, and atrial fibrillation), or patients receiving drugs that prolong the QT interval. Use ciprofloxacin with caution in patients with other conditions that may increase the risk of QT prolongation including congenital long QT syndrome, myocardial infarction, hypertension, coronary artery disease, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, patients with diabetes, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation. Silent mutations and genetic polymorphisms in potassium channels may further increase the risk of QT prolongation in patients taking fluoroquinolones. If a fluoroquinolone is desired in patients with risk factors for QT prolongation, the use of ciprofloxacin with ECG monitoring at initiation of therapy may be recommended. If other quinolones are used, ECG and/or Holter monitoring during therapy may be recommended.

Systemic quinolones have been associated with disabling and potentially irreversible serious neurotoxicity, including central nervous system effects and peripheral neuropathy. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Because of this risk for serious and potentially permanent side effects, quinolones should only be used for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis in cases where alternative treatment options cannot be used. Avoid quinolone use in patients who have previously experienced peripheral neuropathy. Additionally, use quinolones with caution in patients with a known or suspected CNS disorder (e.g., seizure disorder, severe cerebrovascular disease) or in the presence of other risk factors (e.g., certain drug therapy, renal dysfunction) that may predispose to seizures or lower seizure threshold. Therapy should be discontinued at the first signs or symptoms of neuropathy (e.g., pain, burning, tingling, numbness, weakness, or other alterations of sensation such as light touch, temperature, position sense, and vibratory sensation) or central nervous system adverse events (i.e., anxiety, confusion, convulsions, depression, hallucinations, severe headaches, increased intracranial pressure (including pseudotumor cerebri), insomnia, lightheadedness, nightmares, paranoia, restlessness, suicidal thoughts or acts, toxic psychosis, or tremors).

Myasthenia gravis

Avoid systemic quinolones, like ciprofloxacin, in patients with a history of myasthenia gravis. Quinolones may exacerbate the signs of myasthenia gravis and lead to life threatening weakness of the respiratory muscles. Serious postmarketing events, including deaths and the requirement for ventilatory support, have been associated with quinolone use in patients with myasthenia gravis. Because of this risk for serious and potentially permanent side effects, quinolones should only be used for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis in cases where alternative treatment options cannot be used.

Diabetes mellitus

Disturbances of blood glucose have been reported in patients with diabetes mellitus who were receiving an oral hypoglycemic agent or insulin concomitantly with systemic quinolone antibiotics, like ciprofloxacin. Careful monitoring of blood glucose is recommended. Patients with diabetes may also be at an increased risk of developing detachment of the retina.

Dialysis, renal disease, renal failure, renal impairment

Use systemic ciprofloxacin with caution in patients with renal disease. Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Some modification of dosage is recommended in patients with renal impairment, including those with severe renal dysfunction or renal failure, and in patients receiving dialysis.

Dehydration

Systemic ciprofloxacin should be used with caution in patients who have dehydration. Crystalluria related to systemic use has been reported only rarely in humans because human urine is usually acidic. Alkalinization of the urine should be avoided in patients receiving ciprofloxacin. Hydrate patients well; hydration may help prevent the formation of highly concentrated urine and prevent crystalluria.

Hepatic disease, hepatitis, hepatotoxicity, jaundice

Use caution when administering ciprofloxacin to patients at risk for or with a preexisting history of hepatic disease. Ciprofloxacin has been associated with severe hepatotoxicity, including hepatic necrosis and hepatic failure (both fatal and non-fatal). Ciprofloxacin-induced hepatotoxicity is often associated with hypersensitivity, has a rapid onset (1 to 39 days), and may be hepatocellular, cholestatic or mixed. Of note, most patients experiencing fatal outcomes have been over the age of 55 years; therefore, caution is advised in older adults. Immediately discontinue use if signs and symptoms of hepatitis (e.g., anorexia, jaundice, dark urine, pruritus, abdominal pain) develop during treatment.

Sunlight (UV) exposure

Patients receiving systemic ciprofloxacin and other fluoroquinolones have experienced phototoxic reactions. Moderate to severe photosensitivity/phototoxicity reactions can occur after being exposed to direct or indirect sunlight or to artificial ultraviolet light (e.g., sunlamps) during or after treatment with ciprofloxacin. Phototoxic reactions are characterized by an exaggerated sunburn reaction (e.g., burning, erythema, exudation, vesicles, blistering, edema) in areas exposed to light such as the face, the neck, extensor surfaces of the forearms, and dorsa of the hands. Patients should avoid direct or indirect artificial ultraviolet light or sunlight (UV) exposure (even when using sunscreens) during and for several days after ciprofloxacin therapy. Ciprofloxacin therapy should be discontinued immediately at the first signs of phototoxicity.

Almost all antibacterial agents, including systemic ciprofloxacin, have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over 2 months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

Pregnancy

There are no adequate and well-controlled studies of systemic ciprofloxacin use during human pregnancy. Ciprofloxacin crosses the placenta. An expert review of published data examined the effect of ciprofloxacin in women exposed to the drug during the first trimester. This review reported that usual doses of ciprofloxacin during pregnancy are not likely to cause teratogenic effects, however the reviewed data were insufficient to conclude that there was no risk. Two prospective studies followed women exposed to fluoroquinolones during pregnancy. The first study was a controlled prospective observational study which followed 200 women exposed to fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first trimester exposures) during gestation. Exposure to fluoroquinolones during embryogenesis was not associated with increased risk of major malformations. Rates of spontaneous abortions, prematurity and low birth weight did not differ between the groups and there were no clinically significant musculoskeletal dysfunctions up to 1 year of age in ciprofloxacin-exposed pediatric patients. Another prospective follow-up study reported on 549 pregnancies with fluoroquinolone exposure (93% first trimester exposures). There were 70 ciprofloxacin exposures, all within the first trimester. No specific patterns of congenital abnormalities were found. The study did not reveal any clear adverse reactions due to in utero exposure to ciprofloxacin. In both prospective studies, the malformation rates among live-born babies exposed to ciprofloxacin and fluoroquinolones overall were both within background incidence ranges. The available data are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses. Ciprofloxacin should, therefore, not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother. There are no well-controlled studies to inform regarding ophthalmic or otic use of ciprofloxacin during pregnancy; caution is advised.

Breast-feeding

Ciprofloxacin, when given systemically, is excreted into human breast milk; however, the bioavailability in breast milk is unknown. The effect of calcium in breast milk on bioavailability has not been determined, but bioavailability is expected to be reduced based on pharmacokinetic properties of the drug. The manufacturer states that because of the potential for serious adverse reactions (e.g., arthropathy) in the nursing infant, a decision should be made whether to discontinue breast feeding or to discontinue the drug, taking into account the importance of the drug to the mother. One manufacturer states that during short courses of therapy, nursing mothers may express and discard their breast milk and that feeding can resume within 24 hours after the last dose. Following topical otic or ophthalmic administration, systemic absorption has been reported to be less than 5 ng/mL; minimal, if any, ciprofloxacin is expected in breast milk. Levofloxacin, sulfamethoxazole; trimethoprim, ceftazidime, cefepime, and piperacillin; tazobactam may be potential systemic alternatives to consider during breast-feeding. However, site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Antibiotics considered to be usually compatible with breast-feeding by the AAP include ofloxacin, trimethoprim (in combination with sulfamethoxazole), and ceftazidime. Levofloxacin is the S-enantiomer of ofloxacin and although it is excreted in breast milk, the estimated amount that a nursing infant would receive, 1.23 mg/day, is less than doses that have been used to treat an infant. Other beta-lactams, such as cefepime and piperacillin; tazobactam are generally considered compatible with breast-feeding. In a study of lactating women given three oral ciprofloxacin doses of 750 mg, ciprofloxacin breast milk concentrations were higher than serum concentrations with peak concentrations occurring in 2 hours and the lowest concentration occurring at 24 hours; the mean milk:serum ratio varied from 0.85 to 2.14. A case report of a woman receiving 500 mg ciprofloxacin PO nightly for 10 days while breast-feeding concluded that the nursing infant was receiving approximately 0.92 mg/day (0.15 mg/kg/day) with no adverse effects. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Sexually transmitted disease

While ciprofloxacin may be used to treat certain sexually transmitted diseases (STD), the drug may mask or delay the symptoms of incubating syphilis when given as part of an STD treatment regimen. All patients with a diagnosed or suspected STD should be tested for other STDs, which may include HIV, syphilis, chlamydia, and gonorrhea, at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.

Geriatric

Systemic ciprofloxacin should be used cautiously in geriatric patients. Geriatric patients may be more susceptible to drug-associated hepatic and cardiac effects, including effects on the QT interval, and may also be at increased risk for drug-associated tendon effects, especially in those receiving concomitant treatment with corticosteroids. Dosage adjustments are recommended for older adults with renal dysfunction, and renal function monitoring may be useful during therapy. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions. Fluoroquinolones may cause a prolonged QT interval, may increase the risk of acute tendonitis, and may increase the risk of hypoglycemia or hyperglycemia in adults 65 years or older, and in individuals with diabetes, renal sufficiency (CrCl less than 60 mL/minute), or those receiving other glucose-altering medications. Per OBRA, use should be avoided in individuals with prolonged QTc intervals or who are receiving selected anti-arrhythmic agents.

Children, infants, neonates

Caution is warranted when prescribing systemic ciprofloxacin for neonates, infants, children, and adolescents for infections not listed in the approved labeling. According to the FDA-approved product labeling, an increased incidence of adverse reactions compared to controls, including events related to joints and/or surrounding tissues, has been observed. Evidence supporting sustained injury to developing joints in humans is lacking at this time; however, the possibility of rare occurrences has not been excluded. One retrospective study compared the rate of tendon or joint disorders in more than 7,000 pediatric patients less than 19 years old who received ciprofloxacin, ofloxacin, or levofloxacin with more than 20,000 patients who received azithromycin. The incidence of potential tendon or joint disorders was found to be approximately 2% in both the quinolone and azithromycin groups, and verified disorders were reported in less than 1% in both groups. The authors state that this incidence is likely to reflect the background incidence of these disorders in pediatric patients. Ciprofloxacin did not have an effect on linear growth in very low birth weight infants who received the drug. Due to concerns of increasing bacterial resistance, the possibility of rare joint injury, and other possible serious adverse reactions (i.e., CNS effects, peripheral neuropathy), the American Academy of Pediatrics Committee on Infectious Diseases recommends reserving the use of systemic quinolones for infections caused by multidrug-resistant pathogens for which there is no safe and effective alternative, for the treatment of infections when parenteral therapy is not feasible and no other effective oral agent is available, and for the treatment of infections as an alternative to standard therapy because of concerns for antimicrobial resistance, toxicity, or characteristics of tissue penetration.

Contact lenses

Whenever clinical judgment dictates, examine patients receiving ophthalmic ciprofloxacin with the aid of magnification, such as slitlamp biomicroscopy, and where appropriate, fluorescein staining. Advise patients not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.

Driving or operating machinery

Systemic ciprofloxacin can cause dizziness and light-headedness; therefore, patients should know how they react to the drug before driving or operating machinery or engaging in an activity requiring mental alertness or coordination.

DRUG INTERACTIONS

Abarelix: (Moderate) Since abarelix can cause QT prolongation, abarelix should be used cautiously with other drugs that are associated with QT prolongation, such as ciprofloxacin. Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with ciprofloxacin. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors. Acarbose: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Acetaminophen; Butalbital; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium salicylate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Acetaminophen; Codeine: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. Acetaminophen; Dextromethorphan: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Acetaminophen; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Acetazolamide: (Minor) A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If urinary alkalinizing agents such as carbonic anhydrase inhibitors are used concomitantly, the solubility of ciprofloxacin can be decreased because of alkaline urine. Patients should be monitored for crystalluria and nephrotoxicity. Ado-Trastuzumab emtansine: (Major) Avoid concomitant use of ado-trastuzumab emtansine with ciprofloxacin, as plasma exposure to the cytotoxic small molecule of ado-trastuzumab emtansine, DM1, may be increased. Treatment with ado-trastuzumab emtansine should be delayed until ciprofloxacin is cleared from the circulation (approximately 3 elimination half-lives), or an alternate medication with less potential to inhibit CYP3A4 should be considered. If co-administration is necessary, monitor for an increase in ado-trastuzumab emtansine-related adverse events. Ciprofloxacin is a moderate CYP3A4 inhibitor. While formal drug interaction studies have not been conducted, DM1 is mainly metabolized by CYP3A4 (and to a lesser extent, CYP3A5) in vitro. Coadministration may result in potentially increased DM1 exposure and toxicity. Alfentanil: (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate. Alfuzosin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering alfuzosin with ciprofloxacin. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval, like ciprofloxacin. Aliskiren: (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate. Aliskiren; Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate. Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate. Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate. Aliskiren; Valsartan: (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate. Almotriptan: (Major) The plasma concentrations of almotriptan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as serotonergic excess and triptan-related side effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while almotriptan is a CYP3A4 substrate. Alogliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including alogliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Alogliptin; Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including alogliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Alogliptin; Pioglitazone: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including alogliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Alosetron: (Major) Avoid coadministration of alosetron and ciprofloxacin due to the potential for increased exposure and half-life of alosetron. Ciprofloxacin is a strong inhibitor of CYP1A2; alosetron is a CYP1A2 substrate. Coadministration of another strong CYP1A2 inhibitor increased the mean alosetron AUC by about 6-fold and prolonged the half-life by 3-fold. Alpha-glucosidase Inhibitors: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Alprazolam: (Moderate) A decrease in the alprazolam dose may be needed. Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of alprazolam and increase the potential for benzodiazepine toxicity. Aluminum Hydroxide: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide. Aluminum Hydroxide; Magnesium Carbonate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide. (Major) Quinolone antimicrobials can chelate with divalent or trivalent cations. Ciprofloxacin given orally can chelate with such cations. The oral absorption of quinolones will be significantly reduced by other orally administered compounds that contain aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids (e.g., aluminum hydroxide, magnesium hydroxide, calcium carbonate or combination antacids containing aluminum, magnesium or calcium); magnesium citrate; magnesium salicylate; and multivitamins that contain calcium. Other highly buffered drugs may also reduce absorption of ciprofloxacin. It is not yet clear if bismuth subsalicylate (Pepto-Bismol) can interfere with fluoroquinolone bioavailability. Ciprofloxacin should be taken either 2 hours before or 6 hours after taking these agents. Because many foods contain divalent or trivalent cations, food interactions with quinolones may also be significant. Aluminum Hydroxide; Magnesium Hydroxide: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain magnesium hydroxide. (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide. Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain magnesium hydroxide. (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide. Aluminum Hydroxide; Magnesium Trisilicate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide. (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain magnesium trisilicate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Amiodarone: (Major) Concurrent use of amiodarone and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Concomitant use should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Amitriptyline: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Amitriptyline; Chlordiazepoxide: (Major) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity. (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Amlodipine; Atorvastatin: (Major) The risk of developing myopathy during therapy with atorvastatin is increased if coadministered with ciprofloxacin, a CYP3A4 inhibitor. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. Atorvastatin is metabolized by CYP3A4, and coadministration with CYP3A4 inhibitors can lead to an increase in plasma concentrations of atorvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined atorvastatin and ciprofloxacin therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Amlodipine; Benazepril: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Amlodipine; Olmesartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Amlodipine; Telmisartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Amlodipine; Valsartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Amoxicillin; Clarithromycin; Lansoprazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with ciprofloxacin. Clarithromycin is associated with an established risk for QT prolongation and TdP. Ciprofloxacin has a possible risk for QT prolongation and TdP and should be used cautiously with clarithromycin. Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with ciprofloxacin. Clarithromycin is associated with an established risk for QT prolongation and TdP. Ciprofloxacin has a possible risk for QT prolongation and TdP and should be used cautiously with clarithromycin. (Minor) Concomitant use of ciprofloxacin and omeprazole may decrease the AUC and Cmax of ciprofloxacin, but the clinical significance of this interaction is unknown. Codministration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin. A single 1000 mg oral dose of Cipro XR administered with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers resulted in a decrease in the ciprofloxacin mean AUC by 20% and Cmax by 23%. However, coadministration of a single 1000 mg oral dose of Proquin XR given 2 hours after the third dose of omeprazole (40 mg once daily for 3 days) to 27 healthy volunteers resulted in no changes in the ciprofloxacin AUC and Cmax. If ciprofloxacin is administered with omeprazole with magnesium, chelation of the ciprofloxacin would be expected; in general, it is recommended that ciprofloxacin be administered 2 hours before or 6 hours after any divalent cations like magnesium to help limit an interaction. Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with anagrelide. In addition, anagrelide is partially metabolized by CYP1A2. Coadministration of anagrelide with drugs that inhibit CYP1A2, such as ciprofloxacin, could theoretically decrease the elimination of anagrelide and increase the risk of side effects or toxicity. Patients should be monitored for increased adverse effects if anagrelide is coadministered with ciprofloxacin. Apomorphine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering apomorphine with ciprofloxacin. Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2 to 10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use due to substantially increased exposure of aprepitant with ciprofloxacin use. If coadministration cannot be avoided, use caution and monitor for an increase in aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. Ciprofloxacin is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with another moderate CYP3A4 inhibitor increased the aprepitant AUC 2-fold; clinically meaningful changes in ECG, heart rate, or blood pressure did not occur. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. Aripiprazole: (Moderate) Caution is advised when administering aripiprazole with ciprofloxacin, as use of these drugs together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In addition, rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Arsenic Trioxide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering arsenic trioxide with ciprofloxacin. If possible, use of ciprfloxacin should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Artemether; Lumefantrine: (Major) Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, such as ciprofloxacin, coadministration may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with other drugs that prolong the QT interval should be avoided. Consider ECG monitoring if ciprofloxacin must be used with or after artemether; lumefantrine treatment. (Major) Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, such as ciprofloxacin, coadministration may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with other drugs that prolong the QT interval should be avoided. Consider ECG monitoring if ciprofloxacine must be used with or after artemether; lumefantrine treatment. Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer, asenapine should not be used with other agents also known to have this effect. Ciprofloxacin is associated with a possible risk for QT prolongation and torsade de pointes; therefore, caution is advised during combination therapy. In addition, in vitro studies indicate that CYP1A2 is a primary metabolic pathway of asenapine. In theory, inhibitors of this isoenzyme such as ciprofloxacin may decrease the elimination of asenapine. Aspirin, ASA; Butalbital; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. Aspirin, ASA; Omeprazole: (Minor) Concomitant use of ciprofloxacin and omeprazole may decrease the AUC and Cmax of ciprofloxacin, but the clinical significance of this interaction is unknown. Codministration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin. A single 1000 mg oral dose of Cipro XR administered with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers resulted in a decrease in the ciprofloxacin mean AUC by 20% and Cmax by 23%. However, coadministration of a single 1000 mg oral dose of Proquin XR given 2 hours after the third dose of omeprazole (40 mg once daily for 3 days) to 27 healthy volunteers resulted in no changes in the ciprofloxacin AUC and Cmax. If ciprofloxacin is administered with omeprazole with magnesium, chelation of the ciprofloxacin would be expected; in general, it is recommended that ciprofloxacin be administered 2 hours before or 6 hours after any divalent cations like magnesium to help limit an interaction. Atomoxetine: (Moderate) Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of TdP. Atorvastatin: (Major) The risk of developing myopathy during therapy with atorvastatin is increased if coadministered with ciprofloxacin, a CYP3A4 inhibitor. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. Atorvastatin is metabolized by CYP3A4, and coadministration with CYP3A4 inhibitors can lead to an increase in plasma concentrations of atorvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined atorvastatin and ciprofloxacin therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. Atorvastatin; Ezetimibe: (Major) The risk of developing myopathy during therapy with atorvastatin is increased if coadministered with ciprofloxacin, a CYP3A4 inhibitor. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. Atorvastatin is metabolized by CYP3A4, and coadministration with CYP3A4 inhibitors can lead to an increase in plasma concentrations of atorvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined atorvastatin and ciprofloxacin therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. Avanafil: (Moderate) Caution should be used when prescribing avanafil to patients receiving concomitant moderate CYP3A4 inhibitors including ciprofloxacin. During coadministration, the maximum recommended dose of avanafil is 50 mg, not to exceed once every 24 hours. Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Another CYP3A4 inhibitor increased avanafil Cmax and AUC equal to approximately 2-fold and 3-fold, respectively, and prolonged the half-life of avanafil to approximately 8 hours. Axitinib: (Moderate) Use caution if coadministration of axitinib with ciprofloxacin is necessary, due to the risk of increased axitinib-related adverse reactions. Axitinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2, CYP2C19, and UGT1A1. Ciprofloxacin inhibits CYP3A4 and CYP1A2 activity. Coadministration with a strong CYP3A4/5 inhibitor, significantly increased the plasma exposure of axitinib in healthy volunteers. The manufacturer of axitinib recommends a dose reduction in patients receiving strong CYP3A4 inhibitors, but recommendations are not available for moderate or weak CYP3A4 inhibitors. Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc. Azelastine; Fluticasone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Azithromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and ciprofloxacin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Concurrent use may increase the risk of QT prolongation. Bacillus Calmette-Guerin Vaccine, BCG: (Major) Ciprofloxacin may interfere with the effectiveness of Bacillus Calmette-Guerin Live, BCG. The TheraCys product is made from the Connaught strain of Bacillus Calmette and Guerin, which is an attenuated strain of Mycobacterium bovis. Sensitivity of the Connaught strain to several antibiotics was tested in vitro. Bacteria were susceptible to ciprofloxacin. Urinary concentrations of these antibiotics could interfere with the therapeutic effectiveness of BCG. Furthermore, the minimum inhibitory concentrations associated with each drug render them potentially useful for the treatment of systemic BCG reactions or infections. Although the TICE BCG product is obtained from a different strain (Tice strain), similar antimicrobial sensitivities may occur. Postpone instillation of BCG if the patient is receiving antibiotics. BCG Live should not be used in patients with an active infection (see Contraindications).[ Bedaquiline: (Major) Coadministration of bedaquiline with other QT prolonging drugs, such as ciprofloxacin, may result in additive or synergistic prolongation of the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Bendamustine: (Major) Bendamustine is metabolized to minimally active metabolites by CYP1A2. Concurrent administration of a CYP1A2 inhibitor such as ciprofloxacin may increase bendamustine concentrations in plasma. Caution should be exercised, or alternative treatments considered, when coadministering bendamustine with a CYP1A2 inhibitor. Bepridil: (Major) Bepridil is associated with a well-established risk of QT prolongation and torsades de pointes. Patients receiving other drugs which have the potential for QT prolongation, such as ciprofloxacin, have an increased risk of developing proarrhythmias during bepridil therapy. Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include ciprofloxacin. Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include ciprofloxacin. Boceprevir: (Moderate) Close clinical monitoring is advised when administering ciprofloxacin with boceprevir due to an increased potential for boceprevir-related adverse events. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of ciprofloxacin and boceprevir. Ciprofloxacin is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated. Bortezomib: (Minor) Plasma concentrations of bortezomib may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as gastrointestinal side effects, hypotension, or peripheral neuropathy, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while bortezomib is a CYP3A4 substrate. Bosentan: (Moderate) Coadministration of bosentan, a CYP3A4 substrate, with ciprofloxacin, a CYP3A4 inhibitor, may increase the plasma concentrations of bosentan. No dosage adjustment of bosentan is needed, however, the potential for increased bosentan effects, such as hepatic injury or decreased blood pressure, should be monitored. Bosutinib: (Major) Avoid concomitant use of bosutinib and ciprofloxacin; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor. Brentuximab vedotin: (Moderate) Clinical monitoring for adverse effects, such as peripheral neuropathy or gastrointestinal side effects, is recommended during coadministration of brentuximab vedotin and ciprofloxacin. Plasma concentrations of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin, may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while MMAE is a CYP3A4 substrate. Brexpiprazole: (Moderate) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Ciprofloxacin is a moderate inhibitor of CYP3A4. If ciprofloxacin is used in combination with brexpiprazole and a moderate to strong CYP2D6 inhibitor, the brexpiprazole dose should be adjusted and the patient should be carefully monitored for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a moderate CYP3A4 inhibitor. Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of ciprofloxacin. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ciprofloxacin is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively. Brompheniramine; Dextromethorphan; Guaifenesin: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Brompheniramine; Guaifenesin; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Budesonide: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Budesonide; Formoterol: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Bupivacaine Liposomal: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate. Bupivacaine: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate. Bupivacaine; Lidocaine: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate. (Moderate) Concomitant use of systemic lidocaine and ciprofloxacin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ciprofloxacin inhibits both of these isoenzymes. In a study of healthy volunteers (n = 9), concomitant use of lidocaine (1.5mg/kg IV) and ciprofloxacin (500 mg twice daily) resulted in an increase of lidocaine Cmax and AUC by 12% and 26%, respectively. Buprenorphine: (Major) Buprenorphine should be used cautiously and with close monitoring with ciprofloxacin. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Additionally, the plasma concentrations of buprenorphine and its metabolite, norbuprenorphine, may be elevated when administered concurrently ciprofloxacin. Dose adjustments are not required; however clinical monitoring for adverse effects, such as CNS side effects or respiratory depression, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while buprenorphine is a CYP3A4 substrate. Buprenorphine; Naloxone: (Major) Buprenorphine should be used cautiously and with close monitoring with ciprofloxacin. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Additionally, the plasma concentrations of buprenorphine and its metabolite, norbuprenorphine, may be elevated when administered concurrently ciprofloxacin. Dose adjustments are not required; however clinical monitoring for adverse effects, such as CNS side effects or respiratory depression, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while buprenorphine is a CYP3A4 substrate. Buspirone: (Moderate) Close clinical monitoring is recommended if buspirone is administered with ciprofloxacin; buspirone dose reductions may be required. The plasma concentrations of buspirone may be elevated when administered concurrently with ciprofloxacin. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. Ciprofloxacin is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of buspirone. These drugs used in combination may result in elevated buspirone plasma concentrations, causing an increased risk for buspirone-related adverse events. Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Caffeine; Ergotamine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Calcium Carbonate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Calcium Carbonate; Magnesium Hydroxide: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain magnesium hydroxide. (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Calcium Carbonate; Risedronate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Calcium Salts: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Calcium: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Calcium; Vitamin D: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Canagliflozin; Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Carbamazepine: (Major) Serum carbamazepine concentrations should be monitored closely during coadministration with ciprofloxacin; reduced carbamazepine doses may be necessary. Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as ciprofloxacin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Carbetapentane; Guaifenesin; Phenylephrine: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc. Carbetapentane; Phenylephrine: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc. Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Carbonic anhydrase inhibitors: (Minor) A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If urinary alkalinizing agents such as carbonic anhydrase inhibitors are used concomitantly, the solubility of ciprofloxacin can be decreased because of alkaline urine. Patients should be monitored for crystalluria and nephrotoxicity. Cariprazine: (Moderate) Monitor for adverse effects, such as CNS effects and extrapyramidal symptoms, during coadministration of cariprazine and ciprofloxacin. Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Ciprofloxacin is a CYP3A4 inhibitor and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied. Celecoxib: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and ciprofloxacin; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Cevimeline: (Moderate) Clinical monitoring for adverse effects, such as GI or cardiac side effects, is recommended during coadministration of cevimeline and ciprofloxacin as the plasma concentrations of cevimeline may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while cevimeline is a CYP3A4 substrate. Chlordiazepoxide: (Major) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity. Chlordiazepoxide; Clidinium: (Major) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity. Chloroquine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering chloroquine with ciprofloxacin. Chloroquine administration is associated with an increased risk of QT prolongation and TdP. The need to coadminister chloroquine with other drugs associated with QT prolongation and TdP, such as ciprofloxacin, should be done with a careful assessment of risks versus benefits and should be avoided when possible. Chlorpheniramine; Codeine: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. Chlorpheniramine; Dextromethorphan: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Chlorpheniramine; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Chlorpheniramine; Pseudoephedrine: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc. Chlorpromazine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering chlorpromazine with ciprofloxacin. Phenothiazines have been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Administration of chlorpromazine with ciprofloxacin may cause additive QT prolongation and could lead to TdP, and therefore concurrent use is generally not recommended. Choline Salicylate; Magnesium Salicylate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium salicylate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chromium: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Cilostazol: (Major) Reduce cilostazol dose to 50 mg PO twice daily when administered with ciprofloxacin. Coadministration of moderate CYP3A4 inhibitors, such as ciprofloxacin, can increase exposure to cilostazol, a CYP3A4 substrate. Cisapride: (Severe) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of ciprofloxacin is contraindicated with cisapride. Citalopram: (Major) Concurrent use of citalopram and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with ciprofloxacin. Clarithromycin is associated with an established risk for QT prolongation and TdP. Ciprofloxacin has a possible risk for QT prolongation and TdP and should be used cautiously with clarithromycin. Clindamycin: (Moderate) Concomitant use of clindamycin and ciprofloxacin may decrease clindamycin clearance and increase the risk of adverse reactions. Clindamycin is a CYP3A4 substrate; ciprofloxacin is a moderate inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together. Clindamycin; Tretinoin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as ciprofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. Clomipramine: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Clonazepam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity. Clopidogrel: (Minor) The therapeutic effectiveness of clopidogrel should be monitored during coadministration with ciprofloxacin. Clopidogrel requires hepatic biotransformation to an active metabolite; the activation is thought to be mediated by the CYP3A4 isoenzyme. Ciprofloxacin is an inhibitor of CYP3A4 and may decrease the hepatic metabolism of clopidogrel to its active metabolite. Clorazepate: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of clorazepate and increase the potential for benzodiazepine toxicity. Clorazepate is a pro-drug converted to N-desmethyldiazepam in the GI tract; N-desmethyldiazepam is metabolized by CYP3A4. Clozapine: (Major) If co-administration of clozapine and a potent inhibitor of CYP1A2 such as ciprofloxacin is necessary, the manufacturer of clozapine recommends using one-third of the usual clozapine dose. If the inhibitor is discontinued, increase the clozapine dose based on clinical response. One study of 7 schizophrenic patients has shown that concurrent therapy with ciprofloxacin (250 mg twice daily) versus placebo resulted in increased clozapine plasma concentrations (29%) and N-desmethylclozapine plasma concentrations (31%). One case study has reported elevated clozapine plasma concentrations (by 80%) during ciprofloxacin coadministration at doses of 500 mg twice daily. In addition, rare cases of QT prolongation and torsade de pointes (TdP) have been reported with both ciprofloxacin and clozapine. Elevated plasma concentrations of clozapine occurring through inhibition of CYP1A2, CYP3A4, or CYP2D6 may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. If quinolone administration is indicated during clozapine therapy, an alternative fluoroquinolone with minimal inhibitory effects on CYP1A2, CYP2D6, or CYP3A4 should be considered. Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic ciprofloxacin therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of ciprofloxacin is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of ciprofloxacin, resume cobimetinib at the previous dose. Use an alternative to ciprofloxacin in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a CYP3A substrate in vitro, and ciprofloxacin is a moderate inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with a strong CYP3A4 inhibitor increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7). Codeine: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. Codeine; Guaifenesin: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. Codeine; Phenylephrine; Promethazine: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include ciprofloxacin. Codeine; Promethazine: (Moderate) Monitor patients for increased opiate-related side effects and adjust the dose of codeine as necessary when used concomitantly with ciprofloxacin. The activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. The CYP3A4 pathway is an important metabolic clearance route for codeine, and inhibition of this metabolic pathway by CYP3A4 inhibitors, such as ciprofloxacin, may lead to elevated codeine concentrations that are available for conversion to morphine by CYP2D6. (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include ciprofloxacin. Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ciprofloxacin unless the use of both agents is imperative. Ciprofloxacin can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate inhibitor like ciprofloxacin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day. Collagenase: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Conivaptan: (Moderate) Coadministration of conivaptan with CYP3A4 inhibitors, such as ciprofloxacin, could lead to an increase in conivaptan serum concentrations. Conivaptan is a substrate of CYP3A4. According to the manufacturer, coadministration of conivaptan with strong CYP3A4 inhibitors is contraindicated. Until further data are available, it is prudent to coadminister conivaptan with caution or to avoid coadministering conivaptan with other drugs known to be significant inhibitors of CYP3A4 isoenzymes, such as ciprofloxacin. Crizotinib: (Major) Monitor ECGs for QT prolongation, monitor electrolytes, and watch for an increase in crizotinib-related adverse reactions (e.g., vision disorders, diarrhea, increased transaminases, and neuropathy) if coadministration with ciprofloxacin is necessary. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib is a CYP3A substrate that has been associated with concentration-dependent QT prolongation. Ciprofloxacin is a moderate CYP3A4 inhibitor; rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Cyanocobalamin, Vitamin B12: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Cyclobenzaprine: (Moderate) Coadministration of ciprofloxacin with drugs known to prolong the QT interval could increase the risk of developing torsade de pointes (TdP) in predisposed patients. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Cyclobenzaprine is associated with a possible risk of QT prolongation and TdP, particularly in the event of acute overdose. Additionally, ciprofloxacin is a CYP3A4 and CYP1A2 inhibitor. Based on in vitro data, the CYP3A4 and CYP1A2 enzymes are primarily responsible for the hepatic metabolism of cyclobenzaprine via N-demethylation in humans. Cyclophosphamide: (Moderate) Use caution if cyclophosphamide is used concomitantly with ciprofloxacin, and monitor for possible changes in the efficacy or toxicity profile of cyclophosphamide. The clinical significance of this interaction is unknown. Cyclophosphamide is a prodrug that is hydroxylated and activated primarily by CYP2B6; the contribution of CYP3A4 to the activation of cyclophosphamide is variable. N-dechloroethylation to therapeutically inactive but neurotoxic metabolites occurs primarily via CYP3A4. It is not yet completely clear what effect inhibitors of CYP2B6 or CYP3A4 have on the activation and/or toxicity of cyclophosphamide; it has been postulated that the use of CYP3A4 inhibitors might attenuate neurotoxic effects of the drug in some patients, but no clinically reliable data are available to support this hypothesis. In vitro, coadministration with a CYP3A4 inhibitor had little-to-no effect on cyclophosphamide metabolism. However, concurrent use of cyclophosphamide conditioning therapy with both strong and moderate CYP3A4 inhibitors in a randomized trial resulted in increases in serum bilirubin and creatinine, along with increased exposure to toxic cyclophosphamide metabolites (n = 197). Cyclosporine: (Moderate) Monitor renal function during concomitant therapy. Cyclosporine serum concentrations should be monitored and suitable dosage adjustments made. Coadministration of ciprofloxacin and cyclosporine may result in elevated plasma cyclosporine concentrations. Cyclosporine is extensively metabolized by CYP3A4; ciprofloxacin is an inhibitor of CYP3A4. Additionally, some quinolones, including ciprofloxacin, have been associated with transient elevations in serum creatinine in patients receiving concomitant cyclosporine and ciprofloxacin therapy and may potentiate renal dysfunction. Cases of nephrotoxicity with and without increases in cyclosporine concentrations during concurrent cyclosporine and ciprofloxacin treatment have been reported. Daclatasvir: (Moderate) According to the manufacturer, concurrent administration of daclatasvir, a CYP3A4 substrate, with ciprofloxacin, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions. Dapagliflozin; Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Dapagliflozin; Saxagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including saxagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Dapsone: (Moderate) Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration of dapsone and ciprofloxacin. Plasma concentrations of dapsone may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate. Darifenacin: (Moderate) Clinical monitoring for adverse effects, such as anticholinergic effects, is recommended during coadministration of darifenacin and ciprofloxacin. The plasma concentrations of darifenacin may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while darifenacin is a CYP3A4 substrate. Darunavir: (Moderate) Caution is warranted when darunavir is administered with ciprofloxacin as there is a potential for elevated concentrations of darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while darunavir is a CYP3A4 substrate. Darunavir; Cobicistat: (Moderate) Caution is warranted when darunavir is administered with ciprofloxacin as there is a potential for elevated concentrations of darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while darunavir is a CYP3A4 substrate. Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Ritonavir has been associated with dose-related QT prolongation in other trials. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used cautiously and with close monitoring with ritonavir. Dasatinib: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering dasatinib with ciprofloxacin. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Ciprofloxacin also has a possible risk for QT prolongation and TdP and should be used cautiously with dasatinib. Daunorubicin: (Major) Ciprofloxacin has been reported to cause QT prolongation and torsade de pointes. Use ciprofloxacin with caution with daunorubicin or doxorubicin as acute cardiotoxicity can occur during administration; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy. Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with ciprofloxacin. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; ciprofloxacin is a moderate inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold. Additionally, coadministration of deflazacort and ciprofloxacin may increase the risk of tendon rupture that has been associated with quinolone antibiotics. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain as these are symptoms that may precede rupture of the tendon. Degarelix: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation, such as ciprofloxacin. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or receiving treatment with ciprofloxacin. Delavirdine: (Moderate) The plasma concentrations of delavirdine may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP3A4 substrate and ciprofloxacin is an inhibitor of CYP3A4. Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Desipramine: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Deutetrabenazine: (Moderate) For patients taking a deutetrabenazine dosage more than 24 mg/day with ciprofloxacin, assess the QTc interval before and after increasing the dosage of either medication. Ciprofloxacin should be used with caution in patients receiving other drugs that prolong the QT interval. Clinically relevant QTc prolongation may occur with deutetrabenazine. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Dexamethasone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Dexlansoprazole: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate. Dextromethorphan: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Dextromethorphan; Guaifenesin: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Dextromethorphan; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include ciprofloxacin. (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Dextromethorphan; Quinidine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering quinidine with ciprofloxacin. Quinidine is associated with QT prolongation and TdP. The manufacturer of dextromethorphan; quinidine recommends an ECG in patients taking it in combination with other drugs known to prolong the QTc, such as ciprofloxacin. (Minor) Plasma concentrations of dextromethorphan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dextromethorphan is a CYP3A4 substrate. Diazepam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of diazepam and increase the potential for benzodiazepine toxicity. Ciprofloxacin has been shown to decrease the clearance and increase the half-life of diazepam. However, no significant changes were observed in digit symbol substitution psychometric tests, tapping rate and short memory, or concentration, vigilance, and tension. Diclofenac: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Diclofenac; Misoprostol: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Didanosine, ddI: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after didanosine tablets or powder for oral solution. Ciprofloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with ciprofloxacin. Diflunisal: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Diltiazem: (Moderate) Caution and monitoring is warranted with the use of ciprofloxacin and diltiazem. Monitor for adverse events such as a decrease in blood pressure or heart rate. Coadministration of ciprofloxacin, a CYP3A4 inhibitor, with diltiazem, a CYP3A4 substrate, may result in elevated diltiazem serum concentrations. Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Diphenhydramine; Ibuprofen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Diphenhydramine; Naproxen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Disopyramide: (Major) Both disopyramide and ciprofloxacin are associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, caution is advised when administering these medications concurrently. Disulfiram: (Moderate) The plasma concentrations of disulfiram may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while disulfiram is a CYP3A4 substrate. Docetaxel: (Moderate) The plasma concentrations of docetaxel may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as myelosuppression and neurologic toxicity, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while docetaxel is a CYP3A4 substrate. Dofetilide: (Severe) Because of the potential for torsade de pointes (TdP), use of dofetilide with ciprofloxacin is contraindicated. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Dolasetron: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering dolasetron with ciprofloxacin. Ciprofloxacin has been associated with a possible risk for QT prolongation and TdP based on varying levels of documentation. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Dolasetron injection is contraindicated for use for the prevention of chemotherapy-induced nausea and vomiting because the risk of QT prolongation is higher with the doses used for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Dolutegravir; Rilpivirine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with ciprofloxacin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include ciprofloxacin. Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include ciprofloxacin. Doxepin: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Doxorubicin: (Major) Avoid coadministration of escitalopram and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity. Ciprofloxacin is a moderate CYP3A4 inhibitor; doxorubicin is a major CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Additionally, acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Ciprofloxacin should be used with caution in patients receiving other drugs that prolong the QT interval. Dronabinol, THC: (Moderate) Use caution if coadministration of dronabinol with ciprofloxacin is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP3A4 substrate; ciprofloxacin is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. Dronedarone: (Severe) Concurrent use of dronedarone and ciprofloxacin is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc, such as ciprofloxacin, may induce Torsade de Pointes (TdP) and is contraindicated. Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as ciprofloxacin. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Duloxetine: (Major) Coadministration of duloxetine and potent inhibitors of CYP1A2, such as ciprofloxacin, should be avoided. Duloxetine is partially metabolized by CYP1A2. One study involving a potent CYP1A2 inhibitor in concomitant use with duloxetine showed that duloxetine exposure was significantly increased. Efavirenz: (Major) Coadministration of efavirenz and ciprofloxacin may increase the risk for QT prolongation and torsades de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and ciprofloxacin may increase the risk for QT prolongation and torsades de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and ciprofloxacin may increase the risk for QT prolongation and torsades de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with ciprofloxacin may cause the plasma concentrations of elbasvir and grazoprevir to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Ciprofloxacin is a moderate inhibitor of CYP3A; both elbasvir and grazoprevir are metabolized by CYP3A. If these drugs are used together, closely monitor for signs of hepatotoxicity. Eletriptan: (Moderate) The plasma concentrations of eletriptan may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as headache and cardiotoxicity, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while eletriptan is a CYP3A4 substrate. Eliglustat: (Major) Coadministration of eliglustat and ciprofloxacin is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with ciprofloxacin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with moderate CYP3A inhibitors, such as ciprofloxacin, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Both eliglustat and ciprofloxacin can independently prolong the QT interval, and coadministration increases this risk. Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inhibitors of CYP1A2, such as ciprofloxacin, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered. Eluxadoline: (Moderate) The effect CYP enzymes have on the metabolism of eluxadoline has not been definitively established; therefore, the manufacturer recommends caution when administering eluxadoline concurrently with stong CYP1A2 inhibitors, such as ciprofloxacin. When administering these drugs together, closely monitor patients for eluxadoline-related side effects, such as impaired mental and physical abilities need to safely drive or operate machinery. Empagliflozin; Linagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including linagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Empagliflozin; Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with ciprofloxacin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with ciprofloxacin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Enalapril; Felodipine: (Moderate) Concurrent administration of felodipine with ciprofloxacin may result in elevated felodipine plasma concentrations. This increase in felodipine concentration may lead to increased therapeutic and adverse effects, such as lower blood pressure, dizziness, and headache. Felodipine is metabolized by the hepatic isoenzyme CYP3A4; ciprofloxacin is an inhibitor of this enzyme. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Enflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Enteral Feedings: (Major) Enteral feedings may decrease the serum concentrations of quinolone antimicrobials. The enteral formulation Ensure significantly decreased the serum concentrations of ciprofloxacin, levofloxacin, and ofloxacin tablets by 83%, 61%, and 46%, respectively, when they were crushed and mixed with 240 ml of Ensure. One study showed that enteral feedings given concurrently with ciprofloxacin via the oral or jejunostomy routes decreased the mean bioavailability of ciprofloxacin by 27 to 67%; however, ciprofloxacin serum concentrations after coadministration with enteral feedings via a gastrostomy tube were similar to concentrations following administration of ciprofloxacin on an empty stomach. Administration of ciprofloxacin and enteral feedings together through a nasogastric (NG) tube decreased the gastrointestinal absorption of ciprofloxacin minimally; MIC values remained high for many pathogenic bacteria. Ciprofloxacin should be taken either 2 hours before or 6 hours after enteral feedings. Epirubicin: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering ciprofloxacin with epirubicin. Ciprofloxacin has been reported to cause QT prolongation and TdP. Acute cardiotoxicity can also occur during administration of epirubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Ciprofloxacin is a CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension. Eribulin: (Major) Concurrent use of eribulin and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation, and ciprofloxacin is associated with a posssible risk for QT prolongation and TdP. Erlotinib: (Major) Avoid the coadministration of erlotinib with ciprofloxacin due to the risk of increased erlotinib-related adverse reactions; if concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2. Ciprofloxacin is a moderate CYP1A2 inhibitor, and a weak inhibitor of CYP3A4 in vitro. In vivo data regarding CYP3A4 inhibition with ciprofloxacin are conflicting, with one study postulating that the in vivo concentrations reached with routine dosing may be below the inhibitory constant for CYP3A4 activity. Coadministration of erlotinib with ciprofloxacin increased the erlotinib AUC by 39% and the Cmax by 17%. Ertugliflozin; Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Ertugliflozin; Sitagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including sitagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Erythromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with ciprofloxacin. Erythromycin is associated with QT prolongation and TdP. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously with erythromycin. Erythromycin; Sulfisoxazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with ciprofloxacin. Erythromycin is associated with QT prolongation and TdP. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously with erythromycin. Escitalopram: (Moderate) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as ciprofloxacin, should be done with caution and close monitoring. Esomeprazole: (Minor) Use caution when administering ciprofloxacin and esomeprazole concurrently. Ciprofloxacin is an inhibitor of CYP3A, and esomeprazole is partially metabolized by CYP3A. Coadministration of ciprofloxacin with CYP3A substrates, such as esomeprazole, can theoretically increase esomeprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. Esomeprazole; Naproxen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. (Minor) Use caution when administering ciprofloxacin and esomeprazole concurrently. Ciprofloxacin is an inhibitor of CYP3A, and esomeprazole is partially metabolized by CYP3A. Coadministration of ciprofloxacin with CYP3A substrates, such as esomeprazole, can theoretically increase esomeprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. Estazolam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity. Ester local anesthetics: (Major) "Quinolones have been associated with QT prolongation and in rare cases, torsades de pointes (TdP).Of the quinolones, ciprofloxacin has the least potential for causing QT prolongation at usual dosages. Rare cases of TdP have been reported with ciprofloxacin during post-marketing surveillance. Although less likely than with most quinolones, coadministration of ciprofloxacin with drugs known to prolong the QT interval could increase the risk of developing TdP in predisposed patients. Other drugs with potential to prolong the QT interval may include local anesthetics. Eszopiclone: (Moderate) Patients should be advised of the potential for next-day psychomotor and/or memory impairment during co-administration of eszopiclone and CYP3A4 inhibitors, such as ciprofloxacin. CYP3A4 is a primary metabolic pathway for eszopiclone, and increased systemic exposure to eszopiclone increases the risk of next-day impairment, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Ethinyl Estradiol; Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as ciprofloxacin may increase the serum concentration of etonogestrel. Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. Ethosuximide: (Moderate) Close clinical monitoring is advised when administering ethosuximide with ciprofloxacin due to an increased potential for ethosuximide-related adverse events. If ethosuximide dose adjustments are made, re-adjust the dose upon completion of ciprofloxacin treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ethosuximide. Ethosuximide is metabolized by the hepatic isoenzyme CYP3A4; ciprofloxacin inhibits this isoenzyme. Coadministration may result in elevated ethosuximide plasma concentrations. Etodolac: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as ciprofloxacin may increase the serum concentration of etonogestrel. Etoposide, VP-16: (Major) The plasma concentrations of etoposide may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as myelosuppression and GI effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while etoposide is a CYP3A4 substrate. Everolimus: (Major) A dose adjustment of everolimus is necessary when prescribed with ciprofloxacin due to increased plasma concentrations of everolimus. For patients with breast cancer, neuroendocrine tumors, renal cell carcinoma, and renal angiolipoma with tubular sclerosis complex (TSC), reduce the dose of Afinitor to 2.5 mg once daily; consider increasing the dose to 5 mg based on patient tolerance. For patients with subependymal giant cell astrocytoma (SEGA) with TSC, the recommended starting dose of Afinitor/Afinitor Disperz is 2.5 mg/m2 once daily, rounded to the nearest tablet strength; subsequent dosing should be guided by therapeutic drug monitoring, with administration every other day if dose reduction is required for patients receiving the lowest available tablet strength. If ciprofloxacin is discontinued, increase everolimus to its original dose after a washout period of 2 to 3 days. Zortress dosing for prophylaxis of organ rejection should be guided by TDM. Everolimus is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Ezetimibe; Simvastatin: (Moderate) Monitor for evidence of myopathy, including rhabdomyolysis, during coadministration of ciprofloxacin and simvastatin. There are case reports of rhabdomyolysis in patients stabilized on a simvastatin regimen after the addition of ciprofloxacin. Ciprofloxacin may increase simvastatin exposure. Simvastatin is a substrate for CYP3A4; ciprofloxacin is a moderate CYP3A4 inhibitor. Ezogabine: (Major) Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval, such as ciprofloxacin. Famotidine; Ibuprofen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Felodipine: (Moderate) Concurrent administration of felodipine with ciprofloxacin may result in elevated felodipine plasma concentrations. This increase in felodipine concentration may lead to increased therapeutic and adverse effects, such as lower blood pressure, dizziness, and headache. Felodipine is metabolized by the hepatic isoenzyme CYP3A4; ciprofloxacin is an inhibitor of this enzyme. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Fenoprofen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Fentanyl: (Moderate) The plasma concentrations of fentanyl may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while fentanyl is a CYP3A4 substrate. Ferric Citrate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after ferric citrate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Fingolimod: (Major) Cautious use of fingolimod with ciprofloxacin is advised, as ciprofloxacin is associated with a possible risk for QT prolongation and torsade de pointes. Fingolimod initiation results in decreased heart rate and may prolong QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of TdP. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Flecainide: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering ciprofloxacin with flecainide. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as ciprofloxacin, may have an increased risk of developing proarrhythmias. Flibanserin: (Severe) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as ciprofloxacin, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. Fluconazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering fluconazole with ciprofloxacin. Fluconazole has been associated with QT prolongation and rare cases of TdP. Ciprofloxacin also has a possible risk for QT prolongation and TdP and should be used cautiously with fluconazole. Fluocinolone; Hydroquinone; Tretinoin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as ciprofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include ciprofloxacin. Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include ciprofloxacin. (Major) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP) including ciprofloxacin. Additionally, ciprofloxacin inhibits the activity of CYP1A2. Inhibitors of CYP1A2 could potentially reduce the elimination of olanzapine. However, since multiple enzyme pathways metabolize olanzapine, inhibition of only one isoenzyme may not appreciably decrease olanzapine clearance. One case study reported elevated olanzapine plasma concentrations during ciprofloxacin coadministration, possibly due to CYP1A2 inhibition of olanzapine metabolism. Ciprofloxacin inhibits the activity of CYP1A2. Inhibitors of CYP1A2 could potentially reduce the elimination of olanzapine. However, since multiple enzyme pathways metabolize olanzapine, inhibition of only one isoenzyme may not appreciably decrease olanzapine clearance. One case study reported elevated olanzapine plasma concentrations during ciprofloxacin coadministration, possibly due to CYP1A2 inhibition of olanzapine metabolism. Fluphenazine: (Minor) Both fluphenazine and ciprofloxacin are associated with a possible risk for QT prolongation; therefore, caution is advised when administering these medications concurrently. Flurazepam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of flurazepam and increase the potential for benzodiazepine toxicity. Flurbiprofen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Flutamide: (Moderate) Coadministration of ciprofloxacin and flutamide could lead to increases in the serum concentrations of flutamide. Ciprofloxacin has been shown to inhibit CYP1A2 and CYP3A4 and flutamide is a substrate of these enzymes. Fluticasone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Fluticasone; Salmeterol: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Fluticasone; Umeclidinium; Vilanterol: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Fluticasone; Vilanterol: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Fluvoxamine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and ciprofloxacin. Cases of QT prolongation and TdP have been reported during postmarketing use of both fluvoxamine and ciprofloxacin. Food: (Major) Do not administer oral ciprofloxacin with dairy products (e.g., milk, yogurt) or calcium-fortified juices alone; however, oral ciprofloxacin may be taken with a meal that contains these products. The absorption of oral ciprofloxacin may be decreased if taken with calcium-containing foods or beverages. Fosamprenavir: (Minor) Concomitant use of ciprofloxacin and fosamprenavir may result in increased amprenavir, the active metabolite of fosamprenavir, concentrations. Ciprofloxacin is a CYP3A4 inhibitor and amprenavir is a CYP3A4 substrate. Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as ciprofloxacin. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Rare cases of QT prolongation and TdP have also been reported with ciprofloxacin during postmarketing surveillance. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment. In addition, use of ciprofloxacin with foscarnet may increase the risk of seizures. Since foscarnet is not metabolized by the liver and since renal dysfunction was not present, it is unlikely that drug accumulation is responsible for seizures. An additive effect is proposed since seizures have been associated with ciprofloxacin and foscarnet independently. Fosphenytoin: (Moderate) Use ciprofloxacin and fosphenytoin together with caution as ciprofloxacin has been reported to both increase and decrease phenytoin concentrations. Monitor phenytoin serum concentrations and response to therapy during and shorty after coadministration to avoid the loss of seizure control associated with decreased phenytoin levels and to prevent overdose-related adverse events upon the discontinuation of ciprofloxacin. Gemifloxacin: (Major) Both ciprofloxacin and gemifloxacin are quinolone antibiotics and coadministration would represent duplicate therapy. Additionally, coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Ciprofloxacin is associated with a possible risk for QT prolongation and TdP, and gemifloxacin may also prolong the QT interaval. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and ciprofloxacin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Glipizide; Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Glyburide; Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Goserelin: (Moderate) Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with goserelin include ciprofloxacin. Granisetron: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with ciprofloxacin. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with other potentially QT prolonging drugs, such as ciprofloxacin, may result in clinical consequences. Green Tea: (Moderate) Some, but not all, green tea products contain caffeine. Ciprofloxacin can inhibit the hepatic clearance of caffeine and theobromine which are commonly found in coffee and tea. Caffeine toxicity can result and can manifest as nausea/vomiting, nervousness, anxiety, tachycardia, or seizures. Guaifenesin; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Guanfacine: (Major) Ciprofloxacin may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends decreasing the guanfacine dosage to half the recommended dose if these agents are taken together. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. Upon ciprofloxacin discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and ciprofloxacin is a moderate CYP3A4 inhibitor. Guarana: (Moderate) Reduction or limitation of the guarana or caffeine dosages in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine, which is an active constituent of guarana. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. Halofantrine: (Major) Quinolones have been associated with QT prolongation and in rare cases, torsades de pointes. Of the quinolones, ciprofloxacin has the least potential for causing QT prolongation at usual dosages. Halofantrine has the potential to prolong the QT interval and should be used in caution when administered with ciprofloxacin. Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Haloperidol: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering haloperidol with ciprofloxacin. QT prolongation and TdP have been observed during haloperidol treatment, and ciprofloxacin is associated with a possible risk of QT prolongation and TdP. Excessive haloperidol doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Halothane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Hetastarch; Dextrose; Electrolytes: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. Homatropine; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Hydrochlorothiazide, HCTZ; Quinapril: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after quinapril tablets, which contain magnesium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Hydrochlorothiazide, HCTZ; Triamterene: (Minor) Triamterene is a substrate for CYP1A2. Theoretically, the metabolism of triamterene may be affected by drugs that are inhibitors CYP1A2, such as ciprofloxacin. Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Hydrocodone; Ibuprofen: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Hydrocodone; Potassium Guaiacolsulfonate: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and ciprofloxacin are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized to norhydrocodone via CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ciprofloxacin, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and ciprofloxacin. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Ciprofloxacin should be used with caution in patients receiving other drugs that prolong the QT interval. Hydroxyprogesterone: (Moderate) Concomitant use of ciprofloxacin with hydroxyprogesterone may result in increased serum concentrations of hydroxyprogesterone. Hydroxyprogesterone is a substrate of the hepatic isoenzyme CYP3A4; ciprofloxacin is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ciprofloxacin. Ibrutinib: (Major) If coadministered with ciprofloxacin, reduce the ibrutinib dose to 140 mg/day PO for the treatment of B-cell malignancy or 420 mg/day PO for the treatment of chronic graft-versus-host disease. Resume ibrutinib at the previous dose if ciprofloxacin is discontinued. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection); interruption of ibrutinib therapy or a dose reduction may be necessary in patients who develop severe toxicity. Ibrutinib is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A4 inhibitor, the Cmax and AUC values of ibrutinib were increased by 3.4-fold and 3-fold, respectively. Ibuprofen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Ibuprofen; Oxycodone: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Ibuprofen; Pseudoephedrine: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Ibutilide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering ibutilide with ciprofloxacin. Ibutilide can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as ciprofloxacin. Idarubicin: (Moderate) Ciprofloxacin has been reported to cause QT prolongation and torsade de pointes. Use ciprofloxacin with caution with daunorubicin, doxorubicin, epirubicin, and idarubicin as acute cardiotoxicity can occur during administration; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy. Ifosfamide: (Moderate) The concomitant use of ifosfamide, a CYP3A4 substrate, and ciprofloxacin, a moderate CYP3A4 inhibitor, may decrease the metabolism of ifosfamide to its active metabolite, 4-hydroxy-ifosfamide. As a result of this interaction, ifosfamide treatment effectiveness may be reduced. Iloperidone: (Major) Concurrent use of iloperidone and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Iloperidone has been associated with QT prolongation; however, TdP has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should not be used with other agents also known to have this effect. Ciprofloxacin has been associated with a possible risk for QT prolongation and TdP. Imatinib: (Moderate) Increased imatinib serum levels and toxicity may result with concurrent use of ciprofloxacin. Close monitor patients for any signs of toxicity, such as meylosuppression, fluid retention, and bleeding. Ciprofloxacin may inhibit the metabolism of imatinib via CYP3A4 inhibition. Imipramine: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Incretin Mimetics: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the incretin mimetics, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Indinavir: (Moderate) Use caution with the coadministration of ciprofloxacin and indinavir. The plasma concentrations of indinavir may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor and may decrease the systemic clearance of indinavir, a CYP3A4 substrate. Indomethacin: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with ciprofloxacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Insulins: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including insulins, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Iron Salts: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. Iron: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with ciprofloxacin may result in increased serum concentrations of isavuconazonium. Caution and close monitoring for adverse effects, such as hepatotoxicity, are advised if these drugs are used together. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate CYP3A4; ciprofloxacin is an inhibitor of this enzyme. Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) It may be necessary to adjust the dosage of ciprofloxacin if given concurrently with rifampin. Rifampin may induce the metabolism of ciprofloxacin; coadministration may result in decreased ciprofloxacin plasma concentrations. Ciprofloxacin and rifampin have been used concomitantly in some cases for the treatment of MRSA. Isoniazid, INH; Rifampin: (Moderate) It may be necessary to adjust the dosage of ciprofloxacin if given concurrently with rifampin. Rifampin may induce the metabolism of ciprofloxacin; coadministration may result in decreased ciprofloxacin plasma concentrations. Ciprofloxacin and rifampin have been used concomitantly in some cases for the treatment of MRSA. Isradipine: (Moderate) Coadministration of ciprofloxacin, a CYP3A4 inhibitor, with isradipine, a CYP3A4 substrate, may result in elevated isradipine serum concentrations. If used concurrently, close clinical monitoring of blood pressure is advised. Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include ciprofloxacin. Ivabradine: (Major) Avoid coadministration of ivabradine and ciprofloxacin as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; ciprofloxacin inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances. Ivacaftor: (Moderate) If ciprofloxacin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose, but reduce the frequency to once daily (e.g., if the usual dosage is 150 mg twice daily, reduce to 150 mg once daily). Ivacaftor is a CYP3A4 substrate, and ciprofloxacin is a moderate inhibitor of this enzyme. Coadministration with another moderate CYP3A4 inhibitor, increased ivacaftor exposure by 3-fold. Ixabepilone: (Moderate) Caution is recommended if ixabepilone is coadministered with ciprofloxacin; closely monitor patients for ixabepilone-related toxicities, such as peripheral neuropathy, GI effects, or myelosuppression. Ixabepilone is a CYP3A4 substrate, and concomitant use with moderate CYP3A4 inhibitors such as ciprofloxacin has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include ciprofloxacin. Ketoprofen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Ketorolac: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Lansoprazole; Naproxen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Lanthanum Carbonate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after lanthanum carbonate. When oral quinolones are given for short courses, consider eliminating the lanthanum carbonate doses that would be normally scheduled near the time of quinolone intake. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. The bioavailability of ciprofloxacin was decreased by approximately 50% when coadministered with lanthanum carbonate. Lapatinib: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering lapatinib with ciprofloxacin. Lapatinib can prolong the QT interval, and ciprofloxacin has been associated with a potential risk for QT prolongation and TdP. Leflunomide: (Moderate) Closely monitor for ciprofloxacin-induced side effects such as nausea, vomiting, diarrhea, or abdominal pain when these drugs are used together. In some patients, a dosage reduction of ciprofloxacin may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with ciprofloxacin, a substrate of OAT3, may increase ciprofloxacin plasma concentrations. Lenvatinib: (Major) Lenvatinib should be used cautiously and with close monitoring with ciprofloxacin. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects. Leuprolide: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include ciprofloxacin. Leuprolide; Norethindrone: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include ciprofloxacin. Levobupivacaine: (Moderate) Levobupivacaine is metabolized by cytochrome P450 (CYP) isoenzymes 3A4 and 1A2. Known inhibitors of CYP1A2, such as ciprofloxacin, may result in increased systemic levels of levobupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of levobupivacaine may be needed. Levofloxacin: (Major) Both ciprofloxacin and levofloxacin are quinolone antibiotics and coadministration would represent duplicate therapy. Additionally, coadministration may also increase the risk for QT prolongation and torsade de pointes (TdP). Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have also been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. Levomethadyl: (Major) Quinolones have been associated with QT prolongation and in rare cases, torsades de pointes. Of the quinolones, ciprofloxacin has the least potential for causing QT prolongation at usual dosages. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval, such as levomethadyl. Lidocaine: (Moderate) Concomitant use of systemic lidocaine and ciprofloxacin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ciprofloxacin inhibits both of these isoenzymes. In a study of healthy volunteers (n = 9), concomitant use of lidocaine (1.5mg/kg IV) and ciprofloxacin (500 mg twice daily) resulted in an increase of lidocaine Cmax and AUC by 12% and 26%, respectively. Linagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including linagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Linagliptin; Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including linagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Lithium: (Moderate) Lithium should be used cautiously and with close monitoring with ciprofloxacin. Lithium has been associated with QT prolongation. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Lomitapide: (Severe) Concomitant use of ciprofloxacin and lomitapide is contraindicated. If treatment with ciprofloxacin is unavoidable, lomitapide should be stopped during the course of treatment. Ciprofloxacin is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use. Long-acting beta-agonists: (Moderate) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Loperamide: (Moderate) Loperamide should be used cautiously and with close monitoring with ciprofloxacin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Coadministration may further increase the risk of QT prolongation and TdP. Loperamide; Simethicone: (Moderate) Loperamide should be used cautiously and with close monitoring with ciprofloxacin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Coadministration may further increase the risk of QT prolongation and TdP. Lopinavir; Ritonavir: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering lopinavir; ritonavir with ciprofloxacin. Lopinavir; ritonavir is associated with QT prolongation, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. (Major) Ritonavir has been associated with dose-related QT prolongation in other trials. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used cautiously and with close monitoring with ritonavir. Lumacaftor; Ivacaftor: (Moderate) If ciprofloxacin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose, but reduce the frequency to once daily (e.g., if the usual dosage is 150 mg twice daily, reduce to 150 mg once daily). Ivacaftor is a CYP3A4 substrate, and ciprofloxacin is a moderate inhibitor of this enzyme. Coadministration with another moderate CYP3A4 inhibitor, increased ivacaftor exposure by 3-fold. Magnesium Citrate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium citrate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Magnesium Hydroxide: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain magnesium hydroxide. Magnesium Salicylate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium salicylate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Magnesium Salts: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. Magnesium: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. Maprotiline: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering maprotiline with ciprofloxacin. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs, such as ciprofloxacin. Maraviroc: (Minor) Use caution if coadministration of maraviroc with ciprofloxacin is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and ciprofloxacin is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use. Meclofenamate Sodium: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Mefenamic Acid: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Mefloquine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering mefloquine with ciprofloxacin. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Meglitinides: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the meglitinides, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Melatonin: (Moderate) CYP1A2 inhibitors such as ciprofloxacin and enoxacin may increase melatonin exposure. Melatonin is primarily metabolized by CYP1A2, with lesser contributions by CYP1A1, CYP2C9 and CYP2C19. Meloxicam: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Meperidine; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include ciprofloxacin. Mequinol; Tretinoin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as ciprofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. Metformin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Metformin; Pioglitazone: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Metformin; Repaglinide: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Metformin; Rosiglitazone: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Metformin; Saxagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including saxagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Metformin; Sitagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including metformin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including sitagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval, such as ciprofloxacin, should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have also been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Methazolamide: (Minor) A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If urinary alkalinizing agents such as carbonic anhydrase inhibitors are used concomitantly, the solubility of ciprofloxacin can be decreased because of alkaline urine. Patients should be monitored for crystalluria and nephrotoxicity. Methotrexate: (Moderate) Renal tubular transport of methotrexate may be inhibited by coadministration with ciprofloxacin. This may potentially lead to increased methotrexate plasma concentrations and increase the risk of methotrexate associated toxic reactions. Therefore, patients on methotrexate therapy should be carefully monitored when concomitant ciprofloxacin therapy is indicated. Methylprednisolone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Metoclopramide: (Minor) Metoclopramide accelerates the absorption of oral ciprofloxacin. This results in shorter time to reach maximum ciprofloxacin plasma concentrations. No effect was seen on the bioavailability of ciprofloxacin. Metronidazole: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include ciprofloxacin. Mexiletine: (Moderate) Mexiletine is partially metabolized by CYP1A2 isoenzymes. Although more data are needed, ciprofloxacin appears to decrease the hepatic clearance of mexiletine to a modest degree. The mechanism of this interaction may be ciprofloxacin inhibition of CYP1A2. Clinicians should be aware of the potential for mexiletine related adverse reactions. Midazolam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of midazolam and increase the potential for benzodiazepine toxicity. Interactions of this type are most pronounced with oral midazolam. However, the pharmacokinetics of IV midazolam may also be affected to a lesser extent. Midostaurin: (Major) The concomitant use of midostaurin and ciprofloxacin may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Rare cases of QT prolongation and torsade de pointes have been reported with ciprofloxacin during postmarketing surveillance. Mifepristone, RU-486: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and ciprofloxacin should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Ciprofloxacin should be used with caution in patients receiving other drugs that might prolong the QT interval. Miglitol: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and ciprofloxacin. Coadminister with caution. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation. Mitoxantrone: (Major) Chemotherapy including mitoxantrone has been shown to decrease oral absorption of ciprofloxacin, presumably by altering the intestinal mucosa. In 6 cancer patients receiving chemotherapy and after 13 days of chemotherapy, there were decreases in mean maximum serum concentration, in mean time to reach maximum concentration, and in the area under the concentration curve of ciprofloxacin. Concomitant use of mitoxantrone with other quinolones may decrease GI absorption of the quinolone and possibly decrease the antimicrobial effect of the quinolone. The effects of mitoxantrone on the pharmacokinetics of intravenous ciprofloxacin are unclear at this time. Moxifloxacin: (Major) Both ciprofloxacin and moxifloxacin are quinolone antibiotics and coadministration would represent duplicate therapy. Additionally, coadministration may also increase the risk for QT prolongation and torsade de pointes (TdP). Ciprofloxacin is associated with a possible risk for QT prolongation and TdP, and prolongation of the QT interval has also been reported with moxifloxacin. Post-marketing surveillance has identified very rare cases of moxifloxacin-associated ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. Mycophenolate: (Moderate) Drugs that alter the gastrointestinal flora such as ciprofloxacin may interact with mycophenolate by disrupting enterohepatic recirculation. Mycophenolic acid (MPA) is converted to an inactive phenolic glucuronide, MPA glucuronide (MPAG), which undergoes enterohepatic recirculation. Bacteria that express beta-glucuronidase cleave the glucuronide conjugate, which results in liberation of MPA. Normally, two peaks of MPA occur after administration. The first peak occurs after absorption of MPA, and the second peak occurs after cleavage of MPAG by beta-glucuronidase producing bacteria. Antibiotics with activity against such bacteria can reduce the second peak in MPA serum concentrations; interference of MPAG hydrolysis may lead to less MPA available for absorption. A reduction in predose MPA concentrations was noted after ciprofloxacin (500 mg PO twice daily) was administered to 24 patients taking mycophenolate mofetil and tacrolimus for renal transplant prophylaxis. The predose concentration was obtained before the morning dose and 12 hours after the evening mycophenolate dose. The mean MPA predose concentration at baseline was 2.3 mg/L. After 3 days of ciprofloxacin, the mean concentration was 1.5 mg/L. With 7 days of ciprofloxacin, the predose concentration was 1.2 mg/L, and 3 days after the 7-day course, the mean concentration was not significantly different from baseline (2.6 mg/L). A reduction in the MPA predose concentration was also noted among 21 patients who took a 14-day course of ciprofloxacin. Interestingly, the predose concentration rose with continued ciprofloxacin use. The mean predose concentration was 2.3 mg/L at baseline, 1.4 mg/L after 3 days of the antibiotic, 1.5 mg/L after 7 days of the antibiotic, and 1.9 mg/L after 14 days of the antibiotic. In addition to a rise in predose concentrations with continued antibiotic use, some patients did not have a large reduction in their predose concentration. Nine of 44 patients who got a 7-day course of ciprofloxacin or another antibiotic, and 7 of 38 patients who got a 14-day course with either ciprofloxacin or another antibiotic had MPA concentrations on day 3 of antibiotics that were greater than 80% of baseline values. Also, the predose MPA concentration may not accurately represent changes in overall MPA exposure. No deaths, graft losses, acute rejection episodes, or gastrointestinal disturbances were noted throughout the study. A mycophenolate dose increase in response to reduced MPA predose concentrations could cause toxicity in some patients. Of note, the impact of an antibiotic that reduces enterohepatic recirculation of MPA on patients also taking cyclosporine needs investigation; cyclosporine also reduces the enterohepatic recirculation of MPA. Nabumetone: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with ciprofloxacin. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. Naproxen: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Naproxen; Pseudoephedrine: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Naproxen; Sumatriptan: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Neratinib: (Major) Avoid concomitant use of ciprofloxacin with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibition on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inhibitor increased neratinib exposure by 481%. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure. Niacin; Simvastatin: (Moderate) Monitor for evidence of myopathy, including rhabdomyolysis, during coadministration of ciprofloxacin and simvastatin. There are case reports of rhabdomyolysis in patients stabilized on a simvastatin regimen after the addition of ciprofloxacin. Ciprofloxacin may increase simvastatin exposure. Simvastatin is a substrate for CYP3A4; ciprofloxacin is a moderate CYP3A4 inhibitor. Nilotinib: (Major) Concurrent use of nilotinib and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Nilotinib prolongs the QT interval, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. If concurrent administration is unavoidable, the manufacturer of nilotinib recommends interruption of nilotinib treatment. If nilotinib must be continued, closely monitor the patient for QT interval prolongation. Nisoldipine: (Major) Avoid coadministration of nisoldipine with ciprofloxacin due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and ciprofloxacin is a CYP3A4 inhibitor. Nonsteroidal antiinflammatory drugs: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Norfloxacin: (Moderate) Both ciprofloxacin and norfloxacin are quinolone antibiotics and coadministration would represent duplicate therapy. Additionally, coadministration may also increase the risk for QT prolongation and torsade de pointes (TdP). Ciprofloxacin is associated with a possible risk for QT prolongation and TdP, and TdP has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Nortriptyline: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Octreotide: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering octreotide with ciprofloxacin. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide therapy could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Ofloxacin: (Major) Both ciprofloxacin and ofloxacin are quinolone antibiotics and coadministration would represent duplicate therapy. Additionally, coadministration may also increase the risk for QT prolongation and torsade de pointes (TdP). Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Ofloxacin has also been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of TdP. Olanzapine: (Major) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP) including ciprofloxacin. Additionally, ciprofloxacin inhibits the activity of CYP1A2. Inhibitors of CYP1A2 could potentially reduce the elimination of olanzapine. However, since multiple enzyme pathways metabolize olanzapine, inhibition of only one isoenzyme may not appreciably decrease olanzapine clearance. One case study reported elevated olanzapine plasma concentrations during ciprofloxacin coadministration, possibly due to CYP1A2 inhibition of olanzapine metabolism. Ciprofloxacin inhibits the activity of CYP1A2. Inhibitors of CYP1A2 could potentially reduce the elimination of olanzapine. However, since multiple enzyme pathways metabolize olanzapine, inhibition of only one isoenzyme may not appreciably decrease olanzapine clearance. One case study reported elevated olanzapine plasma concentrations during ciprofloxacin coadministration, possibly due to CYP1A2 inhibition of olanzapine metabolism. Olaparib: (Major) Avoid coadministration of olaparib with ciprofloxacin and consider alternative agents with less CYP3A4 inhibition due to increased olaparib exposure. If concomitant use is unavoidable, reduce the dose of olaparib tablets to 150 mg twice daily; reduce the dose of olaparib capsules to 200 mg twice daily. Olaparib is a CYP3A4/5 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Ombitasvir; Paritaprevir; Ritonavir: (Major) Ritonavir has been associated with dose-related QT prolongation in other trials. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used cautiously and with close monitoring with ritonavir. Omeprazole: (Minor) Concomitant use of ciprofloxacin and omeprazole may decrease the AUC and Cmax of ciprofloxacin, but the clinical significance of this interaction is unknown. Codministration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin. A single 1000 mg oral dose of Cipro XR administered with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers resulted in a decrease in the ciprofloxacin mean AUC by 20% and Cmax by 23%. However, coadministration of a single 1000 mg oral dose of Proquin XR given 2 hours after the third dose of omeprazole (40 mg once daily for 3 days) to 27 healthy volunteers resulted in no changes in the ciprofloxacin AUC and Cmax. If ciprofloxacin is administered with omeprazole with magnesium, chelation of the ciprofloxacin would be expected; in general, it is recommended that ciprofloxacin be administered 2 hours before or 6 hours after any divalent cations like magnesium to help limit an interaction. Omeprazole; Sodium Bicarbonate: (Moderate) Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is usually acidic. Avoid alkalinity of the urine in patients receiving ciprofloxacin when possible. A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If sodium bicarbonate is used concomitantly, the solubility of ciprofloxacin might be decreased because of alkaline urine. Patients should be monitored for crystalluria, proper urination,and altered kidney function. Hydrate patients well to prevent the formation of highly concentrated urine. (Minor) Concomitant use of ciprofloxacin and omeprazole may decrease the AUC and Cmax of ciprofloxacin, but the clinical significance of this interaction is unknown. Codministration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin. A single 1000 mg oral dose of Cipro XR administered with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers resulted in a decrease in the ciprofloxacin mean AUC by 20% and Cmax by 23%. However, coadministration of a single 1000 mg oral dose of Proquin XR given 2 hours after the third dose of omeprazole (40 mg once daily for 3 days) to 27 healthy volunteers resulted in no changes in the ciprofloxacin AUC and Cmax. If ciprofloxacin is administered with omeprazole with magnesium, chelation of the ciprofloxacin would be expected; in general, it is recommended that ciprofloxacin be administered 2 hours before or 6 hours after any divalent cations like magnesium to help limit an interaction. Ondansetron: (Major) Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). Among 42 patients receiving a 4 mg bolus dose of intravenous ondansetron for the treatment of postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after antiemetic administration (p < 0.0001). Ondansetron should be administered with caution in patients taking drugs with potential to induce QT prolongation. Rare cases of TdP have been reported with ciprofloxacin during post-marketing surveillance. Although less likely than with most quinolones, coadministration of ciprofloxacin with drugs known to prolong the QT interval could increase the risk of developing TdP in predisposed patients. Additionally ciprofloxacin inhibits the CYP1A2 isoenzyme, while ondansetron is metabolized by hepatic CYP450 drug-metabolizing enzymes (i.e., CYP3A4, CYP2D6, CYP1A2). In theory, ciprofloxacin may change the clearance and, hence, the half-life of ondansetron. Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Osimertinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of ciprofloxacin with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and ciprofloxacin concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Rare cases of QT prolongation TdP have also been reported with ciprofloxacin during postmarketing surveillance. Oxaprozin: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Paliperidone: (Major) Paliperidone has been associated with QT prolongation. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. If coadministration is considered necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include ciprofloxacin. Pantothenic Acid, Vitamin B5: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Pasireotide: (Major) Cautious use of pasireotide and ciprofloxacin is needed, as coadministration may have additive effects on the prolongation of the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Pazopanib: (Major) Concurrent use of pazopanib and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent use is required, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Pentamidine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering pentamidine with ciprofloxacin. Pentamidine has been associated with QT prolongation, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Pentoxifylline: (Moderate) Ciprofloxacin may increase pentoxifylline serum concentrations. It has been proposed that ciprofloxacin reduces hepatic CYP1A2 metabolism of pentoxifylline. Until further data are available, monitoring for increased pentoxifylline side effects (e.g., headache) is prudent when adding ciprofloxacin to pentoxifylline. Perindopril; Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as ciprofloxacin, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when ciprofloxacin is coadministered with amlodipine; therapeutic response should be monitored. Perphenazine: (Minor) Both perphenazine and ciprofloxacin are associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, caution is advised when administering these medications concurrently. Perphenazine; Amitriptyline: (Minor) Both perphenazine and ciprofloxacin are associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, caution is advised when administering these medications concurrently. (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Phenylephrine; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include ciprofloxacin. Phenytoin: (Moderate) Use ciprofloxacin and phenytoin together with caution as ciprofloxacin has been reported to both increase and decrease phenytoin concentrations. Monitor phenytoin serum concentrations and response to therapy during and shorty after coadministration to avoid the loss of seizure control associated with decreased phenytoin levels and to prevent overdose-related adverse events upon the discontinuation of ciprofloxacin. Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as ciprofloxacin. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Coadministration may increase the risk for QT prolongation. Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and CYP1A2 is thought to be a minor metabolic route for pimozide. Elevated pimozide plasma concentrations due to impaired CYP1A2 metabolism may result in QT prolongation and ventricular arrhythmias. Therefore, the use of pimozide with potent CYP1A2 inhibitors such as ciprofloxacin should be avoided until more is known about the safety of these combinations. Although less likely than with most quinolones, coadministration of ciprofloxacin with drugs known to prolong the QT interval could increase the risk of developing TdP in predisposed patients. Rare cases of TdP have been reported with ciprofloxacin during post-marketing surveillance. Pirfenidone: (Major) Avoid concomitant administration of ciprofloxacin and pirfenidone because it increases exposure to pirfenidone. If concurrent use cannot be avoided, it is recommended with the use of ciprofloxacin at a dosage of 750 mg twice daily that the maintenance dose of pirfenidone be reduced to 534 mg PO 3 times daily. Careful monitoring is suggested when ciprofloxacin is used at a dosage of 250 mg or 500 mg daily. Monitor for adverse effects of pirfenidone, like elevated hepatic enzymes, arthralgia, or nausea. Ciprofloxacin is a moderate inhibitor of CYP1A2, and pirfenidone is primarily metabolized by CYP1A2. In a single-dose study, coadministration of pirfenidone 801 mg and ciprofloxacin, which was dosed at 750 mg twice daily from days 2 to 7, on day 6 increased pirfenidone exposure by 81%. Piroxicam: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Polycarbophil: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after calcium polycarbophil. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Polysaccharide-Iron Complex: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. Pomalidomide: (Major) Avoid the concomitant use of pomalidomide and ciprofloxacin; significantly increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If concomitant use is unavoidable, decrease the pomalidomide dose by 50% and monitor for pomalidomide adverse events. Pomalidomide is a CYP1A2 substrate and ciprofloxacin is a strong CYP1A2 inhibitor. In healthy volunteers, the Cmax and AUC values for pomalidomide were increased by 24% and 125%, respectively, when pomalidomide was co-administered with a strong CYP1A2 inhibitor. Posaconazole: (Major) Both posaconazole and ciprofloxacin are associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, caution is advised when administering these medications concurrently. Pramlintide: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including pramlintide, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Prednisolone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Prednisone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include ciprofloxacin. Probenecid: (Minor) Probenecid decreases renal secretion of ciprofloxacin by 50%, resulting in elevated ciprofloxacin serum concentrations and prolonging its half-life. Procainamide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering procainamide with ciprofloxacin. Procainamide is associated with a well-established risk of QT prolongation and TdP, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Prochlorperazine: (Minor) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering prochlorperazine with ciprofloxacin. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Phenothiazines have been reported to prolong the QT interval. Concurrent use of drugs that are associated with a possible risk for QT prolongation and TdP with prochlorperazine should be approached with caution. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include ciprofloxacin. Propafenone: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with ciprofloxacin. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Protriptyline: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Pyridoxine, Vitamin B6: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. Quazepam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of quazepam and increase the potential for benzodiazepine toxicity. Quetiapine: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. If possible, avoid use of quetiapine with other agents associated with a possible risk for QT prolongation and torsade de pointes, including ciprofloxacin Quinapril: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after quinapril tablets, which contain magnesium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Quinidine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering quinidine with ciprofloxacin. Quinidine is associated with QT prolongation and TdP. The manufacturer of dextromethorphan; quinidine recommends an ECG in patients taking it in combination with other drugs known to prolong the QTc, such as ciprofloxacin. Quinine: (Major) Concurrent use of quinine and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Rare cases of QT prolongation and TdP have also been reported with ciprofloxacin during post-marketing surveillance. Ramelteon: (Major) Ramelteon should be administered with caution to patients taking CYP1A2 inhibitors, such as systemic ciprofloxacin. Strong CYP1A2 inhibitors have been shown to have significant interactions with ramelteon, leading to elevated AUC of ramelteon > 190-fold and Cmax > 70-fold. If ciprofloxacin must be administered with ramelteon, monitor the patient closely for toxicity due to elevated ramelteon serum concentrations. Consider if an alternative fluoroquinolone with no CYP1A2 inhibition, like levofloxacin, could be utilized, or, if ramelteon therapy could be temporarily halted during use of ciprofloxacin. Non-systemic ciprofloxacin formulas, like ear drops, do not interact. Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ranolazine include ciprofloxacin. Rasagiline: (Major) Do not exceed a rasagiline dose of 0.5 mg once daily when coadministered with ciprofloxacin. Rasagiline is primarily metabolized by CYP1A2; ciprofloxacin is an inhibitor of this enzyme. Rasagiline plasma concentrations may increase up to 2 fold in patients using concomitant ciprofloxacin leading to increased adverse events. Regadenoson: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering regadenoson with ciprofloxacin. Regadenoson has been associated with QT prolongation, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Ribociclib: (Major) Avoid coadministration of ribociclib with ciprofloxacin due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of ribociclib may be increased resulting in an increase in treatment-related adverse reactions (e.g., neutropenia, QT prolongation). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Concomitant use may increase the risk for QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and ciprofloxacin is a moderate CYP3A4 inhibitor. Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with ciprofloxacin due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of ribociclib may be increased resulting in an increase in treatment-related adverse reactions (e.g., neutropenia, QT prolongation). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Concomitant use may increase the risk for QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and ciprofloxacin is a moderate CYP3A4 inhibitor. Rifampin: (Moderate) It may be necessary to adjust the dosage of ciprofloxacin if given concurrently with rifampin. Rifampin may induce the metabolism of ciprofloxacin; coadministration may result in decreased ciprofloxacin plasma concentrations. Ciprofloxacin and rifampin have been used concomitantly in some cases for the treatment of MRSA. Rilpivirine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with ciprofloxacin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Riluzole: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when coadministered with ciprofloxacin. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when ciprofloxacin, a CYP1A2 inhibitor, is initiated. Risperidone: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering risperidone with ciprofloxacin. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Both risperidone and ciprofloxacin are associated with a possible risk for QT prolongation and TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Ritonavir: (Major) Ritonavir has been associated with dose-related QT prolongation in other trials. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used cautiously and with close monitoring with ritonavir. Rofecoxib: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Romidepsin: (Major) Concurrent use of romidepsin and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is required, appropriate cardiovascular monitoring should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. Romidepsin has been reported to prolong the QT interval and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Ropinirole: (Moderate) Ropinirole is primarily metabolized by CYP1A2. Ropinirole clearance has been shown to be reduced by coadministration of inhibitors of CYP1A2, such as ciprofloxacin. Therefore, if therapy with a drug known to be a potent inhibitor or inducer of CYP1A2 is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Coadministration of ciprofloxacin (500 mg twice daily) with ropinirole (2 mg three times per day) significantly increases ropinirole AUC by 84% on average, and Cmax by 60%. Ropivacaine: (Moderate) Ropivacaine is metabolized to a 3-OH metabolite primarily by CYP1A2 and to a lesser extent to the pipecoloxylidide (PPX) metabolite by CYP3A4. In a double-blind study, ciprofloxacin reduced the mean plasma clearance of ropivacaine by 31% by inhibiting CYP1A2 and increased the formation of PPX by redirecting metabolism to CYP3A4. Saquinavir: (Major) Concurrent use of saquinavir and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. Ciprofloxacin has been associated with a possible risk for QT prolongation and TdP. Saxagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including saxagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Sertraline: (Moderate) There have been postmarketing reports of QT prolongation and torsade de pointes (TdP) during treatment with sertraline and the manufacturer of sertraline recommends avoiding concurrent use with drugs known to prolong the QTc interval. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Sevelamer: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after sevelamer. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. In a study of 15 healthy subjects, the bioavailability of ciprofloxacin was decreased by approximately 50% when coadministered with sevelamer. Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. SGLT2 Inhibitors: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the sodium-glucose co-transporter 2 (SGLT2) inhibitors, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Short-acting beta-agonists: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Sildenafil: (Major) Use caution with coadministration of sildenafil and ciprofloxacin. After concomitant administration of a single oral 50 mg dose of sildenafil with 500 mg of ciprofloxacin to healthy subjects, the mean Cmax and the mean AUC of sildenafil were both increased approximately two-fold. Sildenafil is metabolized principally by the hepatic cytochrome P450 (CYP) 3A4 (major route) and 2C9 (minor route) isoenzymes. In vitro, ciprofloxacin is an inhibitor of the CYP3A4 isoenzyme. Simvastatin: (Moderate) Monitor for evidence of myopathy, including rhabdomyolysis, during coadministration of ciprofloxacin and simvastatin. There are case reports of rhabdomyolysis in patients stabilized on a simvastatin regimen after the addition of ciprofloxacin. Ciprofloxacin may increase simvastatin exposure. Simvastatin is a substrate for CYP3A4; ciprofloxacin is a moderate CYP3A4 inhibitor. Simvastatin; Sitagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including sitagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. (Moderate) Monitor for evidence of myopathy, including rhabdomyolysis, during coadministration of ciprofloxacin and simvastatin. There are case reports of rhabdomyolysis in patients stabilized on a simvastatin regimen after the addition of ciprofloxacin. Ciprofloxacin may increase simvastatin exposure. Simvastatin is a substrate for CYP3A4; ciprofloxacin is a moderate CYP3A4 inhibitor. Sitagliptin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including sitagliptin, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Sodium Bicarbonate: (Moderate) Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is usually acidic. Avoid alkalinity of the urine in patients receiving ciprofloxacin when possible. A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If sodium bicarbonate is used concomitantly, the solubility of ciprofloxacin might be decreased because of alkaline urine. Patients should be monitored for crystalluria, proper urination,and altered kidney function. Hydrate patients well to prevent the formation of highly concentrated urine. Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with ciprofloxacin. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Ciprofloxacin is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4. Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with ciprofloxacin. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Ciprofloxacin is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4. Solifenacin: (Moderate) Solifenacin should be used cautiously with ciprofloxacin. Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Sonidegib: (Major) Avoid the concomitant use of sonidegib and ciprofloxacin; sonidegib exposure may be significantly increased resulting in increased risk of adverse events, particularly musculoskeletal toxicity. If concomitant use cannot be avoided, administer ciprofloxacin for less than 14 days; monitor patients closely for adverse reactions (e.g., elevated serum creatine kinase and serum creatinine levels). Sonidegib is a CYP3A substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Physiologic-based pharmacokinetic (PBPK) simulations indicate a moderate 3A4 inhibitor would increase the sonidegib AUC by 1.8-fold if administered for 14 days and by 2.8-fold if the moderate CYP3A inhibitor is administered with sonidegib for more than 14 days. Sorafenib: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering sorafenib with ciprofloxacin. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Sorafenib has been associated with QT prolongation, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Sotalol: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering sotalol with ciprofloxacin. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Ciprofloxacin has a possible risk for QT prolongation and TdP and should be used cautiously with sotalol. St. John's Wort, Hypericum perforatum: (Moderate) Use St. John's Wort with caution in patients who are also taking drugs known to be photosensitizers, such as ciprofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. Sucralfate: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after sucralfate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with sucralfate. This interaction appears to be the result of chelation by the aluminum content of sucralfate. Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include ciprofloxacin. Sulfonylureas: (Moderate) Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered. Monitor blood glucose when quinolones and antidiabetic agents are coadministered. Sulindac: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of ciprofloxacin with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Suvorexant: (Major) Suvorexant is primarily metabolized by CYP3A, and the manufacturer recommends a dose reduction to 5 mg of suvorexant during concurrent use with moderate CYP3A inhibitors such as ciprofloxacin and a maximum recommended dose of 10 mg/day. Tacrine: (Moderate) Tacrine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Although not studied, tacrine metabolism may be reduced by coadministration with inhibitors of CYP1A2 such as ciprofloxacin. Tacrolimus: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering tacrolimus with ciprofloxacin. Tacrolimus causes QT prolongation, and ciprofloxacin has been associated with a possible risk for QT prolongation and TdP. Tamoxifen: (Moderate) Caution is advised with the concomitant use of tamoxifen and ciprofloxacin due to an increased risk of QT prolongation and torsade de pointes (TdP). Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Rare cases of QT prolongation and torsade de pointes (TdP) have also been reported with ciprofloxacin during postmarketing surveillance. Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and enoxacin or ciprofloxacin. Because tasimelteon is partially metabolized via CYP1A2, use with CYP1A2 inhibitors, such as enoxacin or ciprofloxacin, may increase exposure to tasimelteon and the potential for adverse reactions. Tazarotene: (Moderate) Use tazarotene with caution in patients who are also taking drugs known to be photosensitizers, such as ciprofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. Telavancin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering telavancin with ciprofloxacin. Telavancin has been associated with QT prolongation, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Telithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with ciprofloxacin. Telithromycin is associated with QT prolongation and TdP. Ciprofloxacin has been associated with a possible risk for QT prolongation and TdP. Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ciprofloxacin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; ciprofloxacin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered. Teriflunomide: (Moderate) Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with ciprofloxacin, a substrate of OAT3, may increase ciprofloxacin plasma concentrations. Monitor for increased adverse effects from ciprofloxacin, such as nausea, vomiting, diarrhea, or abdominal pain. Adjust the dose of ciprofloxacin as necessary and clinically appropriate. Tetrabenazine: (Major) Concurrent use of tetrabenazine and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc), and ciprofloxacin has been associated with a possible risk for QT prolongation and TdP. Tezacaftor; Ivacaftor: (Moderate) If ciprofloxacin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose, but reduce the frequency to once daily (e.g., if the usual dosage is 150 mg twice daily, reduce to 150 mg once daily). Ivacaftor is a CYP3A4 substrate, and ciprofloxacin is a moderate inhibitor of this enzyme. Coadministration with another moderate CYP3A4 inhibitor, increased ivacaftor exposure by 3-fold. (Moderate) Monitor patients closely for tezacaftor; ivacaftor-related adverse reactions if coadministration with ciprofloxacin is necessary. Pharmacokinetic data suggest that no dose adjustment is necessary if tezacaftor; ivacaftor is coadministered with ciprofloxacin. However, because ciprofloxacin is a moderate CYP3A inhibitor, there is a potential for increased tezacaftor; ivacaftor exposure and adverse reactions with concurrent use of ciprofloxacin. Of note, FDA-approved labeling generally recommends tezacaftor; ivacaftor dosage adjustment when coadministered with a moderate CYP3A inhibitor (1 tezacaftor/ivacaftor 150 mg tablet every other day in the morning and 1 ivacaftor 150 mg tablet every other day in the morning on alternate days). Theophylline, Aminophylline: (Major) Avoid coadministration of ciprofloxacin and aminophylline due to the potential for increased and prolonged plasma exposure of theophylline. Monitor theophylline concentrations and adjust dosage as appropriate if concurrent administration cannot be avoided. Ciprofloxacin reduces the clearance of theophylline by 31%. Serious and fatal reactions have occurred in patients receiving concurrent ciprofloxacin and theophylline. These reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. Although similar serious adverse reactions have been reported in patients receiving theophylline alone, the possibility that these reactions may be potentiated by ciprofloxacin cannot be eliminated. Ciprofloxacin is CYP1A2 inhibitor, and theophylline is a substrate of CYP1A2. (Major) Avoid coadministration of ciprofloxacin and theophylline due to the potential for increased and prolonged plasma exposure of theophylline. Monitor theophylline concentrations and adjust dosage as appropriate if concurrent administration cannot be avoided. Ciprofloxacin reduces the clearance of theophylline by 31%. Serious and fatal reactions have occurred in patients receiving concurrent ciprofloxacin and theophylline. These reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. Although similar serious adverse reactions have been reported in patients receiving theophylline alone, the possibility that these reactions may be potentiated by ciprofloxacin cannot be eliminated. Ciprofloxacin is CYP1A2 inhibitor, and theophylline is a substrate of CYP1A2. Thiabendazole: (Moderate) Thiabendazole is metabolized by the hepatic cytochrome isoenzyme CYP1A2. It is also a potent inhibitor of CYP1A2. Ciprofloxacin has been shown to inhibit CYP1A2. In theory, coadministration of ciprofloxacin with substrates of CYP1A2, such as thiabendazole, could lead to increases in the serum concentrations of thiabendazole. Thiazolidinediones: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the thiazolidinediones (e.g., rosiglitazone, pioglitazone), are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Thioridazine: (Severe) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, such as ciprofloxacin. Tizanidine: (Severe) The concurrent use of tizanidine and ciprofloxacin is contraindicated due to the risk of tizanidine toxicity, including hypotension, bradycardia, and sedation. Tizanidine is a CYP1A2 substrate, and ciprofloxacin is a strong inhibitor of CYP1A2. In a trial of healthy volunteers, coadministration of ciprofloxacin increased the AUC of tizanidine by 10-fold. Subjects also experienced a significant decrease in blood pressure, increased drowsiness, and increased psychomotor impairment. In addition, both tizanidine and ciprofloxacin are associated with QT prolongation; coadministration would increase the risk of QT prolongation and torsade de pointes (TdP). Tolmetin: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Tolterodine: (Moderate) Tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6. Drugs that are also associated with QT prolongation and have antimuscarinic properties that should be used cautiously and with close monitoring with tolterodine include ciprofloxacin. Toremifene: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering toremifene with ciprofloxacin. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Ciprofloxacin has been associated with a possible risk for QT prolongation and TdP. Trazodone: (Major) Coadministration of ciprofloxacin and trazodone should be avoided. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval. Tretinoin, ATRA: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as ciprofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. Triamcinolone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. Triamterene: (Minor) Triamterene is a substrate for CYP1A2. Theoretically, the metabolism of triamterene may be affected by drugs that are inhibitors CYP1A2, such as ciprofloxacin. Triazolam: (Moderate) A decrease in the triazolam dose may be needed. Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of triazolam and increase the potential for benzodiazepine toxicity. Tricyclic antidepressants: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Trifluoperazine: (Minor) Both trifluoperazine and ciprofloxacin are associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, caution is advised when administering these medications concurrently. Trimipramine: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Triptorelin: (Moderate) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with triptorelin include ciprofloxacin. Ursodeoxycholic Acid, Ursodiol: (Moderate) There has been one case report of reduced serum concentrations of ciprofloxacin after the administration of ursodeoxycholic acid, ursodiol to a patient with hepatobiliary disease. The mechanism of the proposed interaction is uncertain. Valdecoxib: (Moderate) The concomitant administration of quinolones and nonsteroidal antiinflammatory drugs has been reported to increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders or other risk factors that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for NSAID usage if they are also taking a quinolone. Use a quinolone with caution in individuals who take a NSAID concomitantly. Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib. Ciprofloxacin has also been associated with QT prolongation and TdP. If coadministration is necessary, perform more frequent monitoring of the QT interval. An ECG is needed if ciprofloxacin is started. If QTcF is > 500 msec, interrupt vandetanib dosing until the QTcF is < 450 msec; then, vandetanib may be resumed at a reduced dose. Vardenafil: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering ciprofloxacin with vardenafil. Ciprofloxacin has been associated with a possible risk for QT prolongation and TdP. Vardenafil, at therapeutic (10 mg) and supratherapeutic (80 mg) doses, produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). The effects of these drugs on the QT interval should be considered when prescribing the drug. Vemurafenib: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering vemurafenib with ciprofloxacin. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.Vemurafenib has been associated with QT prolongation, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Venetoclax: (Major) Avoid the concomitant use of venetoclax and ciprofloxacin; venetoclax is a substrate of CYP3A4 and ciprofloxacin is a moderate CYP3A4 inhibitor. Consider alternative agents. If concomitant use of these drugs is required, reduce the venetoclax dosage by at least 50% (maximum dose of 200 mg/day). If ciprofloxacin is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. When venetoclax was administered with multiple doses of strong CYP3A4 inhibitors, the Cmax and AUC values of venetoclax were increased significantly. Use of venetoclax and a moderate CYP3A4 inhibitor has not been evaluated. Venlafaxine: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering venlafaxine with ciprofloxacin. Both venlafaxine and ciprofloxacin are associated with a possible risk of QT prolongation; TdP has been reported with post-marketing use. Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with ciprofloxacin. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Rare cases of QT prolongation and TdP have also been reported with ciprofloxacin during post-marketing surveillance. Vorinostat: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering vorinostat with ciprofloxacin. Vorinostat therapy is associated with a risk of QT prolongation, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP. Warfarin: (Major) Concurrent use of warfarin and systemic quinolones may result in an increased PT/INR. Patients receiving this combination should be closely monitored for bleeding adverse effects. Case reports have noted that quinolones have enhanced the effects of warfarin. Other patient specific factors, such as fever, other disease states (i.e., cancer), or other concurrent medication, may play an important role in precipitating this interaction. Zileuton: (Minor) Zileuton is primarily metabolized by CYP1A2. Zileuton metabolism may be reduced by coadministration with inhibitors of CYP1A2 such as ciprofloxacin. Zinc Salts: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc. Zinc: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc. Ziprasidone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including ciprofloxacin. Zolpidem: (Moderate) Avoid coadministration of zolpidem and ciprofloxacin as the combination may potentially lead to an increase in zolpidem exposure. Zolpidem is primarily metabolized by CYP3A4 and to a lesser extent by other isoenzymes, including CYP1A2. Ciprofloxacin is an inhibitor of both enzymes.

PREGNANCY AND LACTATION

Pregnancy

There are no adequate and well-controlled studies of systemic ciprofloxacin use during human pregnancy. Ciprofloxacin crosses the placenta. An expert review of published data examined the effect of ciprofloxacin in women exposed to the drug during the first trimester. This review reported that usual doses of ciprofloxacin during pregnancy are not likely to cause teratogenic effects, however the reviewed data were insufficient to conclude that there was no risk. Two prospective studies followed women exposed to fluoroquinolones during pregnancy. The first study was a controlled prospective observational study which followed 200 women exposed to fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first trimester exposures) during gestation. Exposure to fluoroquinolones during embryogenesis was not associated with increased risk of major malformations. Rates of spontaneous abortions, prematurity and low birth weight did not differ between the groups and there were no clinically significant musculoskeletal dysfunctions up to 1 year of age in ciprofloxacin-exposed pediatric patients. Another prospective follow-up study reported on 549 pregnancies with fluoroquinolone exposure (93% first trimester exposures). There were 70 ciprofloxacin exposures, all within the first trimester. No specific patterns of congenital abnormalities were found. The study did not reveal any clear adverse reactions due to in utero exposure to ciprofloxacin. In both prospective studies, the malformation rates among live-born babies exposed to ciprofloxacin and fluoroquinolones overall were both within background incidence ranges. The available data are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses. Ciprofloxacin should, therefore, not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother. There are no well-controlled studies to inform regarding ophthalmic or otic use of ciprofloxacin during pregnancy; caution is advised.

Ciprofloxacin, when given systemically, is excreted into human breast milk; however, the bioavailability in breast milk is unknown. The effect of calcium in breast milk on bioavailability has not been determined, but bioavailability is expected to be reduced based on pharmacokinetic properties of the drug. The manufacturer states that because of the potential for serious adverse reactions (e.g., arthropathy) in the nursing infant, a decision should be made whether to discontinue breast feeding or to discontinue the drug, taking into account the importance of the drug to the mother. One manufacturer states that during short courses of therapy, nursing mothers may express and discard their breast milk and that feeding can resume within 24 hours after the last dose. Following topical otic or ophthalmic administration, systemic absorption has been reported to be less than 5 ng/mL; minimal, if any, ciprofloxacin is expected in breast milk. Levofloxacin, sulfamethoxazole; trimethoprim, ceftazidime, cefepime, and piperacillin; tazobactam may be potential systemic alternatives to consider during breast-feeding. However, site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Antibiotics considered to be usually compatible with breast-feeding by the AAP include ofloxacin, trimethoprim (in combination with sulfamethoxazole), and ceftazidime. Levofloxacin is the S-enantiomer of ofloxacin and although it is excreted in breast milk, the estimated amount that a nursing infant would receive, 1.23 mg/day, is less than doses that have been used to treat an infant. Other beta-lactams, such as cefepime and piperacillin; tazobactam are generally considered compatible with breast-feeding. In a study of lactating women given three oral ciprofloxacin doses of 750 mg, ciprofloxacin breast milk concentrations were higher than serum concentrations with peak concentrations occurring in 2 hours and the lowest concentration occurring at 24 hours; the mean milk:serum ratio varied from 0.85 to 2.14. A case report of a woman receiving 500 mg ciprofloxacin PO nightly for 10 days while breast-feeding concluded that the nursing infant was receiving approximately 0.92 mg/day (0.15 mg/kg/day) with no adverse effects. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

MECHANISM OF ACTION

Ciprofloxacin is bactericidal via inhibition of DNA gyrase (topoisomerase II), an enzyme responsible for counteracting the excessive supercoiling of DNA during replication or transcription and topoisomerase IV, an enzyme that helps separate the daughter DNA molecules. In gram-negative bacteria, the primary target is the DNA gyrase A subunit, while the primary target in gram-positive bacteria is generally topoisomerase IV. Ciprofloxacin exhibits concentration-dependent pharmacodynamics. Additionally, ciprofloxacin and other fluoroquinolones exhibit a prolonged post-antibiotic effect (PAE) for gram-negative organisms.

PHARMACOKINETICS

Ciprofloxacin is administered orally as extended-release tablets, immediate-release tablets, oral suspension, and intravenously as an infusion. It is also administered via the ophthalmic and otic routes.

Plasma protein binding is low (20—40%) and the antibiotic is widely distributed into most tissues. Tissue concentrations often exceed serum concentrations, particularly in genital tissue, including the prostate. Penetration into CSF is minimal (< 10% of peak serum concentrations) when meninges are not inflamed. Concentrations are present in the saliva, nasal and bronchial secretions, mucosa of the sinuses, sputum, skin blister fluid, lymph, peritoneal fluid, bile, prostatic secretions, lung, skin, fat, muscle, cartilage, and bone. Low concentrations have been detected in the aqueous and vitreous humors of the eye.

Four metabolites of ciprofloxacin have been identified in human urine, which account for approximately 15% of the oral dose: oxociprofloxacin (M3), sulfociprofloxacin (M2), desethylene ciprofloxacin (M1), and formylciprofloxacin (M4). M3 and M2 are the primary metabolites while M1 and M4 are minor metabolites. All have antimicrobial activity, but are less active than unchanged ciprofloxacin. Ciprofloxacin is eliminated via renal and nonrenal routes. Roughly 35—50% of an orally administered dose is excreted in urine as unchanged drug. In patients with normal renal function, the elimination half-life is approximately 4 hours. Fecal excretion of the drug and its metabolites accounts for 20—35% of the dose. Approximately 1—2% of the dose is recovered in the bile as unchanged drug.

Affected cytochrome P450 isoenzymes: CYP1A2, possibly CYP3A4Ciprofloxacin is an inhibitor of the CYP1A2 isoenzyme. Coadministration with other drugs primarily metabolized by CYP1A2 may result in increased plasma concentrations, and potentially clinically significant pharmacodynamic side effects, of the coadministered drug. In vitro, ciprofloxacin is an inhibitor of the CYP3A4 isoenzyme; however, data from in vivo studies are conflicting. One study postulated that in vivo concentrations usually reached with routine dosing may be consistently below the inhibition constant for CYP3A4 activity.

Oral Route

Following oral administration of immediate-release tablets or suspension, ciprofloxacin hydrochloride is rapidly absorbed from the GI tract and undergoes minimal first-pass metabolism. The absolute bioavailability is approximately 70%. Peak serum concentrations ranging from 1.6—2.9 mcg/mL are reached in 1—2 hours after a 500 mg oral dose. Serum concentrations increase proportionately with doses up to 1000 mg. A 500 mg oral dose given every 12 hours produces an AUC similar to a dose of 400 mg IV every 12 hours; a 750 mg oral dose given every 12 hours produces an AUC similar to a dose of 400 mg IV every 8 hours; and a 250 mg oral dose given every 12 hours produces a similar AUC to a dose of 200 mg IV every 12 hours. When the immediate-release tablets are given with food, the time to peak concentration is delayed (e.g., 2 hours after dosing rather than 1 hour); there is no delay when the oral suspension is given with food. The overall absorption of ciprofloxacin from immediate-release tablets or suspension is not substantially affected by food.

Cipro XR extended-release tablets consist of two parts, an immediate-release component and a slow-release matrix. The immediate-release portion contains approximately 35% of the dose as ciprofloxacin hydrochloride and the slow-release portion contains the remaining 65% as ciprofloxacin. Peak plasma concentrations occur between 1 and 4 hours after dosing. Compared to the 250 mg immediate-release tablets twice daily, Cipro XR extended-release tablets produce a higher Cmax (1.14 mg/L vs 1.59 mg/L) with an equivalent AUC. Cipro XR extended-release tablets may be administered with or without food (e.g., high-fat and low-fat meals or under fasted condition).

Intravenous Route

The pharmacokinetics of ciprofloxacin are linear over the dose range of 200—400 mg IV. There is no evidence of drug accumulation.

Other Route(s)

Ophthalmic RouteAdministration of the ciprofloxacin ophthalmic preparations should not result in clinically significant plasma concentrations. After ophthalmic solution administration, the maximum plasma concentration is < 5 ng/mL and the mean concentration is usually < 2.5 ng/mL.

Otic RouteAdministration of the ciprofloxacin otic preparation should not result in clinically significant plasma concentrations. The plasma concentrations of the otic preparation have not been measured; however, the manufacturer anticipates that plasma concentrations should be < 5 ng/mL.

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